{"paper_id":"0b0acb42-71f7-44dc-a600-bd2012b3fd8f","body_text":"The Comparative Evaluation of the Therapeutic Effects of Autologous Cytokine-Rich Serum and Platelet-Rich Plasma in an Experimental Endometriosis Model | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article The Comparative Evaluation of the Therapeutic Effects of Autologous Cytokine-Rich Serum and Platelet-Rich Plasma in an Experimental Endometriosis Model Erol KARAKAŞ, Mustafa ERMIŞ, Hanifi EROL, Gökhan AKÇAKAVAK, Nevzat Emre ASLAN, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6874729/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: This study aimed to comparatively evaluate the therapeutic effects of Autologous Cytokine-Rich Serum (ACRS) and Platelet-Rich Plasma (PRP) in a rat model of endometriosis, with a focus on inflammation, angiogenesis, and myofibroblast activity. Methods: A total of 36 adult female Wistar Albino rats were randomly assigned to six groups: healthy control, ACRS-only, PRP-only, endometriosis (EM), EM + ACRS, and EM + PRP. Endometriosis was surgically induced in the relevant groups. ACRS and PRP were prepared from the animals' autologous blood and administered intraabdominally. After treatment, endometriotic implants were excised for histopathological scoring and immunohistochemical analysis targeting TNF-α, IL-6 (inflammation), VEGFA (angiogenesis), and α-SMA (myofibroblast activity). Results: Histopathological scores significantly decreased in both EM + ACRS and EM + PRP groups compared to the EM group. ACRS demonstrated superior anti-inflammatory effects, with greater reductions in TNF-α and IL-6 expression than PRP. However, ACRS-treated tissues showed higher VEGFA and α-SMA expression, suggesting enhanced angiogenic and fibrotic responses relative to PRP. Conclusions: Both ACRS and PRP exerted therapeutic effects in experimental endometriosis. ACRS was more effective in reducing inflammation but showed distinct effects on angiogenesis and fibrosis compared to PRP. These findings support the potential of ACRS as a novel therapeutic option, warranting further clinical investigation. Biological sciences/Biological techniques Biological sciences/Immunology Biological sciences/Molecular biology Health sciences/Diseases Health sciences/Medical research Health sciences/Pathogenesis Endometriosis Autologous Cytokine-Rich Serum (ACRS) Platelet-Rich Plasma (PRP) Inflammation Angiogenesis TNF-α IL-6 VEGFA α-SMA rat Figures Figure 1 Figure 2 INTRODUCTION Endometriosis is an estrogen-dependent, chronic inflammatory disease characterized by the presence of endometrial glands and stroma in ectopic locations outside the uterus, most commonly in the ovaries, peritoneum, and the Douglas pouch. Affecting approximately 10% of women of reproductive age, endometriosis leads to symptoms such as chronic pelvic pain, dysmenorrhea, dyspareunia, dyschezia, and infertility, all of which significantly impair quality of life. Additionally, the disease often shows progressive behavior, and a significant proportion of cases experience recurrence over time ( 1 , 2 ). Although the exact etiopathogenesis of endometriosis remains unclear, the most widely accepted hypothesis is Sampson’s theory of retrograde menstruation. According to this theory, endometrial cells shed during menstruation reflux into the peritoneal cavity via the fallopian tubes, where they implant ectopically. However, since retrograde menstruation occurs in nearly all women, the fact that only certain individuals develop endometriosis suggests that additional factors—such as immune intolerance, cellular adhesion and invasion capacity, an inflammatory microenvironment, and genetic/epigenetic predispositions—may play key roles ( 3 , 4 ). At the molecular level, endometriotic lesions are characterized by elevated expression of proinflammatory cytokines (e.g., TNF-α, IL-1β, IL-6), macrophage infiltration, increased angiogenesis (VEGF), and fibrogenesis ( 5 – 7 ). Under the influence of cytokines, growth factors, and reactive oxygen species, the microenvironment of ectopic endometrial tissue gains proliferative and invasive characteristics, which contribute to disease persistence and progression ( 7 , 8 ). Current treatment strategies for endometriosis primarily include surgical excision and hormonal therapies. However, these approaches have notable limitations. Hormonal treatments often produce menopausal side effects (such as osteoporosis and vasomotor symptoms), making long-term use poorly tolerated, while surgical interventions are invasive and frequently associated with high recurrence rates. Therefore, there is a growing need for more targeted, innovative therapeutic alternatives with minimal side effects that can address the underlying pathogenesis of the disease. In this context, regenerative medicine and biologic therapies have gained increasing attention. Platelet-Rich Plasma (PRP), an autologous product derived from whole blood and enriched with high concentrations of platelets, contains a variety of growth factors (PDGF, VEGF, EGF, TGF-β, IGF) and cytokines involved in wound healing, tissue regeneration, and modulation of inflammation. When applied locally, PRP promotes fibroblast proliferation, stimulates angiogenesis and extracellular matrix synthesis, and modulates immune responses. Currently, it is used therapeutically in various medical fields, including orthopedics, dermatology, urology, and gynecology ( 3 , 4 , 9 ). Another promising biologic therapy developed in recent years is Autologous Cytokine-Rich Serum (ACRS), which is produced by incubating autologous blood under specific conditions for several hours, resulting in a serum enriched particularly with anti-inflammatory cytokines (IL-1ra, IL-4, IL-10). ACRS is notably rich in IL-1 receptor antagonist (IL-1ra), which plays a critical role in suppressing the inflammatory response ( 5 , 6 ). Its clinical efficacy has been demonstrated in chronic inflammatory conditions such as osteoarthritis, musculoskeletal disorders, and neuropathic pain ( 5 , 6 ). The anti-inflammatory, antifibrotic, and regenerative properties of both PRP and ACRS align with the pathophysiological mechanisms of endometriosis ( 3 , 4 , 7 , 8 ). However, their potential effects in endometriosis, a complex and inflammation-driven disease, remain inadequately explored. Thus, investigating and comparing the therapeutic efficacy of PRP and ACRS in endometriosis from a molecular perspective is of considerable importance. The aim of this study was to comparatively evaluate the effects of intraovarian administration of PRP and ACRS on inflammation (TNF-α, IL-6), angiogenesis (VEGFA), and fibrosis (α-SMA) in an experimentally induced model of endometriosis. In this context, the study analyzed the potential of these two therapeutic agents to modulate the molecular pathogenesis of endometriosis and explored their viability as novel preclinical treatment options ( 10 ). MATERIALS AND METHODS This study was conducted at the Erciyes University Experimental Research and Application Center (DEKAM) with the approval of the Erciyes University Local Animal Ethics Committee (HADYEK, Decision No: 24/023). All experimental procedures were carried out in accordance with international guidelines for the care and use of laboratory animals. ARRIVE Guidelines Compliance Statement: This study was conducted and reported in accordance with the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines ( https://arriveguidelines.org ). All procedures involving animals were reviewed and approved by the Erciyes University Animal Experiments Local Ethics Committee (HADYEK) on February 7, 2024 (Decision No: 24/023). Every effort was made to minimize animal suffering and the number of animals used. Female Wistar Albino rats weighing between 200–300 g and aged 16–24 weeks were used in the study. The animals were obtained from Erciyes University DEKAM. They were housed in disinfected cages in groups of 4–5 per cage, with free access to standard rat chow and water (ad libitum). The animals were maintained under controlled environmental conditions with a 12-hour light/dark cycle. All experimental procedures were performed at the same time of day to avoid circadian variations. Experimental Groups A total of 36 rats were randomly divided into six groups (n = 6 per group) as follows: Group I (Control group) : No intervention was performed. Group II (PRP control group) : Treated with platelet-rich plasma (PRP) only. Group III (ACRS control group) : Treated with autologous cytokine-rich serum (ACRS) only. Group IV (Endometriosis–distilled water group) : Endometriosis was induced, and distilled water was administered. Group V (Endometriosis–PRP group) : Endometriosis was induced, and PRP treatment was administered. Group VI (Endometriosis–ACRS group) : Endometriosis was induced, and ACRS treatment was administered. Additionally, six rats were used as blood donors for the preparation of PRP and ACRS. Endometriosis Model An experimental endometriosis model was established using the technique described by Vernon and Wilson ( 11 ), which has been shown in subsequent studies to closely mimic human endometriosis ( 12 ). General anesthesia was induced with intraperitoneal administration of ketamine (60 mg/kg) and xylazine (10 mg/kg) ( 12 , 13 ). Following anesthesia, the abdominal area was shaved and disinfected with povidone-iodine. A midline laparotomy was performed, and the right uterine horn was sutured to the peritoneal wall using 4/0 PDS to allow for autotransplantation ( 11 ). After the procedure, the fascia and peritoneum were closed with 3/0 PDS sutures, and the skin was closed with 2/0 PGA. To allow for the formation of endometriotic lesions, animals were monitored for 4 weeks postoperatively ( 11 , 12 ). Preparation Protocols for PRP and ACRS For PRP preparation, blood was collected from donor rats via intracardiac puncture under general anesthesia ( 12 , 13 ) and transferred into tubes containing acid-citrate-dextrose (ACD) solution ( 1 ). The samples were centrifuged at 1000 rpm for 10 minutes. After centrifugation, three layers formed: red blood cells at the bottom, a \"buffy coat\" layer in the middle containing platelets, leukocytes, and a small amount of erythrocytes, and platelet-poor plasma at the top. The plasma fraction was carefully aspirated up to the interface layer using a pipette and transferred into a separate sterile tube ( 1 , 8 ). Approximately 6 ml of PRP was obtained from 10 ml of whole blood ( 1 , 8 ). Preparation of ACRS For the preparation of Autologous Cytokine-Rich Serum (ACRS), intracardiac blood was collected from donor rats under general anesthesia and transferred into specialized kit tubes. The blood samples were incubated in a dedicated incubator for 3 hours, followed by centrifugation at 4000 rpm for 5 minutes ( 5 , 6 ). After centrifugation, the serum formed at the top was carefully aspirated using a pipette and transferred into another tube. Approximately 6 mL of ACRS was obtained from 10 mL of blood ( 5 , 6 ). Treatment Protocols In Groups II and III, the rats underwent laparotomy under general anesthesia ( 12 , 13 ), and a single dose of 0.5 mL of PRP or ACRS was administered directly into the right ovary via intraovarian injection ( 1 , 5 ). This was followed by two additional intraperitoneal injections of 0.5 mL PRP or ACRS at one-week intervals ( 1 ). In Groups IV, V, and VI, after endometriosis model induction and a 4-week period for lesion development ( 11 , 12 ), a laparotomy was performed under general anesthesia ( 12 , 13 ). A single dose of 0.5 mL of distilled water (Group IV), PRP (Group V), or ACRS (Group VI) was administered intraovarianly to the right ovary ( 1 , 5 ). Subsequently, two additional doses of 0.5 mL distilled water, PRP, or ACRS were administered intraperitoneally at one-week intervals ( 1 , 5 ). At the end of the study (Day 31 for the control groups and Day 45 for the endometriosis groups), all rats were sacrificed under anesthesia with xylazine (10 mg/kg) and ketamine (60 mg/kg) via cervical dislocation ( 12 ). The abdominal cavities were opened, and endometriotic lesions and relevant tissue samples were collected for histopathological and immunohistochemical analysis (11,12.14). Histopathological and Immunohistochemical Analysis Uterine tissue samples collected post-necropsy were fixed in 10% neutral buffered formalin ( 12 ). Following fixation, tissues underwent routine histological processing and were embedded in paraffin blocks. Sections of 4–5 µm thickness were cut from the paraffin blocks, stained with hematoxylin and eosin (H&E), and examined under a light microscope (Olympus BX51, Tokyo, Japan) ( 12 , 13 , 25 ). For the histopathological evaluation, the endometriosis grading system previously described was employed ( 11 , 12 , 14 , 26 ). According to this system, tissue samples were semi-quantitatively scored by a blinded pathologist as follows: 0: No epithelial lining 1: Poorly preserved epithelium (epithelial cells present only occasionally) 2: Moderately preserved epithelium with leukocyte infiltration 3: Well-preserved epithelial layers For immunohistochemical analysis, sections from paraffin blocks were subjected to deparaffinization and rehydration. Immunohistochemical staining was performed using a commercial kit (UltraVision Large Volume Detection System Anti-Polyvalent, HRP, TP-060-HL) according to the manufacturer’s instructions ( 12 ). The following primary antibodies were used: α-SMA (alpha-smooth muscle actin, Affinity Biosciences, AF1032, dilution 1:200) ( 8 ) TNF-α (Tumor necrosis factor-alpha, Santa Cruz Biotechnology, sc-133192, dilution 1:400) ( 8 ) IL-6 (Interleukin-6, Affinity Biosciences, DF6087, dilution 1:400) ( 8 ) VEGFA (Vascular Endothelial Growth Factor A, Affinity Biosciences, AF5131, dilution 1:200) ( 8 ) DAB (3,3'-diaminobenzidine) was used as the chromogen, and counterstaining was performed with Mayer’s hematoxylin ( 12 ). Immunohistochemical scoring was conducted semi-quantitatively by a blinded pathologist based on staining intensity and extent: 0 (none), 1 (mild), 2 (moderate), and 3 (strong) ( 27 ). Statistical Analysis Statistical analysis of data was performed using the nonparametric Kruskal–Wallis test. Pairwise comparisons between groups were conducted using the Mann–Whitney U test. A p-value < 0.05 was considered statistically significant. All analyses were performed using appropriate statistical software. RESULTS Histopathological examination revealed that uterine tissues in the control groups (Groups I, II, and III) exhibited normal histological architecture (Fig. 1 .A-B-C). In the endometriosis-induced groups (Groups IV, V, and VI), glandular epithelial hyperplasia, secretions within endometrial gland lumens, inflammatory cell infiltration in the stroma, and numerous macrophages with hemosiderin-laden cytoplasm were observed (Fig. 1 .D-F). In the endometriosis-ACRS group (Group VI), the frequency and severity of lesions were found to be reduced compared to the endometriosis-distilled water group (Group IV). Endometriosis grading scores were lowest in Group IV compared to the control groups (Groups I, II, and III), and this difference was statistically significant. In Group VI, which received ACRS treatment, endometriosis scores were significantly increased compared to Group IV (Table 1 ). Table 1 Endometriosis grading and immunohistochemical scores among groups (Mean ± SE). Group-I Group-II Group-III Group-IV Group-V Group-VI Endometriosis grading 3.00 ± 0.00 a 2.83 ± 0.17 a 2.83 ± 0.17 a 1.33 ± 0.21 c 1.67 ± 0.21 c 2.33 ± 0.21 ab α-SMA 1.83 ± 0.30 ab 2.00 ± 0.36 a 2.00 ± 0.36 a 1.33 ± 0.21 b 1.50 ± 0.22 b 2.33 ± 0.21 a VEGFA 1.67 ± 0.33 ab 1.83 ± 0.40 a 1.83 ± 0.30 a 1.17 ± 0.17 b 1.33 ± 0.21 b 2.17 ± 0.30 a IL-6 0.17 ± 0.17 c 0.33 ± 0.21 c 0.50 ± 0.22 c 2.50 ± 0.22 a 1.83 ± 0.17 b 1.33 ± 0.21 b TNF- α 0.33 ± 0.21 c 0.33 ± 0.21 c 0.50 ± 0.22 c 2.33 ± 0.21 a 1.67 ± 0.21 b 1.17 ± 0.17 b a−d Letters in the same row indicate statistically significant differences between groups (p < 0.001). Immunohistochemical staining (Fig. 2 ) showed that VEGFA and α-SMA expression scores were lowest in Group IV and highest in Group VI. ACRS treatment in Group VI significantly increased VEGFA and α-SMA immunoreactivity compared to Group IV, indicating that ACRS therapy enhances angiogenesis and myofibroblast activity. For TNF-α and IL-6 immunostaining, the lowest scores were observed in the control groups (Groups I, II, and III), whereas the highest scores were detected in the endometriosis-distilled water group (Group IV). Both PRP (Group V) and ACRS (Group VI) treatments significantly reduced TNF-α and IL-6 expressions compared to Group IV. This reduction was more pronounced in the ACRS-treated group. These findings suggest that ACRS treatment may be more effective than PRP in suppressing the inflammatory response. DISCUSSION Endometriosis is a complex, estrogen-dependent inflammatory disease that causes significant symptoms such as chronic pelvic pain, dysmenorrhea, and infertility in women, negatively affecting quality of life. The multifactorial etiology of the disease and its tendency to recur often lead to the inadequacy of current treatment approaches. Although surgical excision and hormonal therapies aim to suppress the disease, their long-term success rates are relatively low, and recurrent symptoms are frequently observed in many cases ( 15 ). In this context, regenerative medicine-based biological treatment approaches such as platelet-rich plasma (PRP) and autologous cytokine-rich serum (ACRS) have attracted attention for their potential in modulating inflammation and supporting tissue regeneration ( 16 ). In this study, the effects of ACRS and PRP treatments on an experimental endometriosis model were evaluated comparatively. Both treatments demonstrated therapeutic effects on the lesions; however, these effects appear to occur through different molecular mechanisms. Effects on the Inflammatory Response It is well-established that immune dysregulation and chronic inflammation play a central role in the pathogenesis of endometriosis ( 17 ). Particularly, elevated levels of pro-inflammatory cytokines such as TNF-α and IL-6 in peritoneal fluid and endometriotic lesions emphasize the importance of inflammation in disease progression ( 18 ). In our study, significantly increased levels of these cytokines were observed in the untreated group with induced endometriosis, confirming the pathophysiological validity of the model. Both ACRS and PRP treatments significantly reduced TNF-α and IL-6 expression levels, indicating that both biological agents have anti-inflammatory potential. However, the decrease was more pronounced in the ACRS-treated group, suggesting that ACRS may have a stronger anti-inflammatory effect. This could be attributed to the presence of potent anti-inflammatory cytokines in ACRS, such as IL-1 receptor antagonist (IL-1Ra), IL-4, and IL-10 ( 19 ). These findings suggest that ACRS may be a promising treatment option targeting the inflammatory component of endometriosis, potentially providing symptomatic relief. Effects on Angiogenesis and Myofibroblast Activity The persistence of endometriotic lesions is not only associated with inflammation but also with processes such as angiogenesis and fibrosis ( 20 ). VEGFA has been identified as a key factor responsible for the vascularization of endometriotic foci. α-SMA is an indicator of myofibroblast activity and fibrotic tissue remodeling, and it may play a role in the chronic persistence of lesions ( 21 ). In our study, ACRS treatment significantly increased both VEGFA and α-SMA expression. This indicates that ACRS not only suppresses inflammation but may also stimulate tissue regeneration and vascular remodeling. However, it should be noted that this increase could facilitate structural stability of the lesions rather than regression, potentially increasing the risk of recurrence in the long term. These findings underscore the need for further experimental studies to evaluate the potential proliferative effects of ACRS before clinical application. On the other hand, PRP treatment induced more limited changes in VEGFA and α-SMA expression levels. This suggests that although PRP is rich in growth factors, its cytokine composition may differ from that of ACRS and possibly be more balanced ( 22 ). This property of PRP may lead to a more controlled therapeutic response by moderately supporting both inflammation modulation and tissue remodeling. Clinical Implications and Evaluation of Treatment Options Histopathological scoring of endometriosis revealed significant differences among treatment groups. Particularly, the higher scores observed in the ACRS group suggest better preservation of lesion structures. This may point to ACRS's tissue-supportive effects; however, it should also be considered that such protective effects might hinder lesion regression. From a clinical perspective, ACRS may contribute to symptom relief by suppressing inflammatory processes, while PRP, due to its more limited effect on angiogenesis and balanced cytokine profile, might present a safer and more conservative therapeutic option that is less likely to promote lesion persistence ( 23 ). Based on these results, PRP could be considered a more balanced and safer biological agent for endometriosis treatment, whereas ACRS may be preferable in cases where inflammation suppression is a primary goal. Nonetheless, these suggestions require further support through advanced preclinical and clinical studies on human tissues before being integrated into clinical practice. Study Limitations and Future Perspectives The limitations of this study include the small sample size, the focus on only specific biomarkers, and the lack of evaluation of the long-term effects of the treatments. Additionally, the experimental model used in this study only partially reflects human pathophysiology, limiting the generalizability of the findings ( 24 ). Future research should compare different doses and administration regimens of ACRS and PRP and evaluate broader inflammatory, fibrotic, and angiogenic responses at the molecular level. Furthermore, investigating the effects of these treatments on fertility, endometrial receptivity, and oocyte quality is essential for potential clinical translation. CONCLUSION This experimental study is one of the first in the literature to comparatively investigate the therapeutic effects of autologous cytokine-rich serum (ACRS) and platelet-rich plasma (PRP) on endometriosis. Our findings reveal that both biological products exert anti-inflammatory effects on endometriotic lesions; however, the underlying molecular mechanisms differ between the two treatments. In particular, ACRS treatment showed a stronger suppressive effect on the expression of proinflammatory cytokines (TNF-α and IL-6) compared to PRP. Additionally, the increased levels of VEGFA and α-SMA following ACRS application suggest that angiogenesis and myofibroblast activity are more prominently induced by ACRS. This indicates that ACRS not only suppresses inflammation but may also remodel the lesion microenvironment through its biological activity. Similarly, PRP treatment reduced the inflammatory response, though its effects on angiogenesis and fibrotic activity were less pronounced than those of ACRS. This suggests that PRP may exert a more limited but targeted anti-inflammatory effect. In contrast, ACRS appears to offer a more complex mechanism of action by influencing immunomodulatory, regenerative, and cell signaling pathways. In this context, both treatment approaches offer promising potential as alternative biological therapies for the management of endometriosis. However, to fully understand the effects of these biological products on endometriosis, it is essential to further elucidate their mechanisms of action at the cellular and molecular levels, evaluate their long-term outcomes, and identify any possible adverse effects. Furthermore, future translational and clinical studies should focus on whether the combination of PRP or ACRS with standard hormonal or surgical treatments can create a synergistic effect and offer therapeutic benefits in cases of resistant or recurrent endometriosis. Key Findings: Both ACRS and PRP treatments reduced the inflammatory response in an experimental endometriosis model. ACRS more effectively suppressed TNF-α and IL-6 expression compared to PRP, while also increasing VEGFA and α-SMA expression levels. These findings suggest that ACRS plays an active role not only in inflammation control but also in angiogenesis and stromal remodeling processes. Clinical Applications: The data suggest that ACRS and PRP could be considered complementary or alternative treatment options, especially in cases resistant to conventional therapies or in recurrent endometriosis. ACRS, with its potential to modulate immune response and support tissue regeneration, may hold a significant place in future personalized treatment strategies for endometriosis. Future Research: The long-term effects of ACRS and PRP, as well as optimal dosages and application frequencies, need to be established. Evaluating the efficacy of these biological therapies in combination with hormonal treatments or surgical interventions may be crucial in developing next-generation endometriosis treatment protocols. It is recommended that future studies explore their molecular effects, particularly on the TGF-β pathway, macrophage polarization, ECM remodeling, and epithelial-mesenchymal transition (EMT). Declarations Authors contributions: EK conducted the experimental animal studies and drafted the manuscript. EK, HE and NEA performed the experimental design. NEA and HE participated in the review and editing of the manuscript. EK, HE and ME conceived the study, participated in its design and coordination, and assisted in the preparation of the manuscript. GA performed histopathology and statistical analyses. GA and OK performed immunohistochemical staining and analysis. All authors read and approved the final version of the manuscript. Funding Statement: No funding was received for this study. The authors funded the study themselves. Acknowledgement: The authors thank laboratory technicians for their assistance with histological preparations and animal care staff for their support. Ethical Statement: The present study was conducted at the Erciyes University Experimental Research Application and Research Center (DEKAM) with the approval of the Erciyes University Animal Experiments Local Ethics Committee (HADYEK, Decision no: 24/023). Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Data avalibility: All the data are included in the manuscript. References Ding, Y., Bian, X., Jiang, Y., Luo, L. & Li, X. The therapeutic effect of platelet-rich plasma in the treatment of endometriosis: A review of the literature. Gynecol. Endocrinol. 39 (4), 347–353. 10.1080/09513590.2022.2159544 (2023). Pajot, C., De Smedt, J., Langlois, M., Donnez, J. & Dolmans, M. M. Regenerative medicine strategies for the treatment of endometriosis: A systematic review. Reprod. Sci. 28 (8), 2077–2090. 10.1007/s43032-020-00369-4 (2021). Huang, X., Liu, J., Wang, T., Wang, X. & Li, J. Platelet-rich plasma modulates the inflammatory response and promotes tissue regeneration: A potential therapy for endometriosis? Reprod. Sci. 28 (5), 1369–1376. 10.1007/s43032-020-00429-9 (2021). van Buul, G. M. et al. Platelet-rich plasma releasate inhibits inflammatory processes in osteoarthritic chondrocytes. Am. J. Sports Med. 39 (11), 2362–2370. 10.1177/0363546511419278 (2011). Wehling, P. et al. Autologous conditioned serum in the treatment of orthopedic diseases: The orthokine therapy. BioDrugs 21 (5), 323–332. 10.2165/00063030-200721050-00003 (2007). Wehling, P. et al. Clinical responses to cytokine inhibition in arthritis and osteoarthritis. BioDrugs 21 (3), 165–174. 10.2165/00063030-200721030-00002 (2007). Zhu, J. et al. The role of cytokines and growth factors in endometriosis: A review. Reprod. Sci. 25 (4), 497–508. 10.1177/1933719117710340 (2018). Hsu, A. L., Khachikyan, I. & Stratton, P. Inflammation and endometriosis. Semin Reprod. Med. 33 (5), 316–325. 10.1055/s-0035-1557836 (2015). Bulun, S. E. & Endometriosis N Engl. J. Med. ; 360 (3):268–279. doi: 10.1056/NEJMra0804690 (2009). Vercellini, P., Viganò, P., Somigliana, E., Fedele, L. & Endometriosis Pathogenesis and clinical impact. Hum. Reprod. Update . 20 (6), 760–772. 10.1093/humupd/dmu025 (2014). Vernon, M. W. & Wilson, E. A. Studies on the surgical induction of endometriosis in the rat. Fertil. Steril. 44 (5), 684–694. 10.1016/s0015-0282(16)49063-4 (1985). Grümmer, R. Animal models in endometriosis research. Hum. Reprod. Update . 12 (5), 641–649. 10.1093/humupd/dml024 (2006). Cakmak, H. & Taylor, H. S. Implantation failure: Molecular mechanisms and clinical treatment. Hum. Reprod. Update . 17 (2), 242–253. 10.1093/humupd/dmq037 (2011). Zindler, T. et al. Animal models of endometriosis and their application for novel drug development. J. Endometr. Pelvic Pain Disord . 11 (1), 1–8. 10.1177/2284026519831148 (2019). Giudice, L. C., Kao, L. C. & Endometriosis Lancet ; 364 (9447):1789–1799. doi: 10.1016/S0140-6736(04)17403-5 (2004). Marx, R. E. Platelet-rich plasma: evidence to support its use. J. Oral Maxillofac. Surg. 62 (4), 489–496. 10.1016/j.joms.2003.12.003 (2004). Lebovic, D. I., Mueller, M. D. & Taylor, R. N. Immunobiology of endometriosis. Fertil. Steril. 75 (1), 1–10. 10.1016/S0015-0282(00)01656-0 (2001). Gazvani, R. & Templeton, A. Peritoneal environment, cytokines and angiogenesis in the pathophysiology of endometriosis. Reproduction 123 (2), 217–226. 10.1530/rep.0.1230217 (2002). Andrade, P. Z., dos Santos, F., da Silva, C. L. & Cabral, J. M. Mesenchymal stem cell therapy for inflammatory diseases: mechanisms, challenges, and opportunities. Cell. Mol. Life Sci. 72 (8), 1403–1420. 10.1007/s00018-014-1792-1 (2015). Donnez, J., Smoes, P., Gillerot, S., Casanas-Roux, F. & Nisolle, M. Vascular endothelial growth factor (VEGF) in endometriosis. Hum. Reprod. 13 (6), 1686–1690. 10.1093/humrep/13.6.1686 (1998). Meuleman, C., Tomassetti, C. & D'Hooghe, T. Clinical outcome after CO2 laser laparoscopy in patients with minimal to moderate endometriosis. Fertil. Steril. 96 (4), 912–916. 10.1016/j.fertnstert.2011.07.1102 (2011). Anitua, E., Sánchez, M., Orive, G. & Andía, I. The potential impact of the preparation rich in growth factors (PRGF) in different medical fields. Biomaterials 28 (31), 4551–4560. 10.1016/j.biomaterials.2007.06.037 (2007). Chang, Y., Chen, Y., Wu, J. & Chen, S. Platelet-rich plasma for treating endometriosis: an in vivo animal study. Taiwan. J. Obstet. Gynecol. 57 (4), 541–545. 10.1016/j.tjog.2018.06.006 (2018). Borghese, B. et al. Research models of endometriosis. Int. J. Dev. Biol. 62 (1-2-3), 159–169. 10.1387/ijdb.170247fb (2018). Kazak, F. et al. Proanthocyanidin alleviates testicular torsion/detorsion-induced ischemia/reperfusion injury in rats. Tissue Cell. 89 , 102459 (2024). Keenan, J. A. et al. Regression of endometrial explants in a rat model of endometriosis treated with the immüne modulators loxoribine and levamisole. Fertil. Steril. 72 (1), 135–141 (1999). Akcakavak, G., Kazak, F. & Yilmaz Deveci, M. Z. Eucalyptol Protects against Cisplatin-Induced Liver Injury in Rats. Biology Bull. 50 (5), 987–994 (2023). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-6874729\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Article\",\"associatedPublications\":[],\"authors\":[{\"id\":492368292,\"identity\":\"6182a52a-c95b-4ef3-89f2-aa530252c618\",\"order_by\":0,\"name\":\"Erol KARAKAŞ\",\"email\":\"data:image/png;base64,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\",\"orcid\":\"\",\"institution\":\"University of Erciyes\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Erol\",\"middleName\":\"\",\"lastName\":\"KARAKAŞ\",\"suffix\":\"\"},{\"id\":492368293,\"identity\":\"cd749b8c-1887-4ff2-9417-adb913ed9c08\",\"order_by\":1,\"name\":\"Mustafa ERMIŞ\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Erciyes\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Mustafa\",\"middleName\":\"\",\"lastName\":\"ERMIŞ\",\"suffix\":\"\"},{\"id\":492368294,\"identity\":\"6cccb43c-aa6d-4574-a71a-b7063c5a6903\",\"order_by\":2,\"name\":\"Hanifi EROL\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Erciyes\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Hanifi\",\"middleName\":\"\",\"lastName\":\"EROL\",\"suffix\":\"\"},{\"id\":492368295,\"identity\":\"efa39d4f-7167-42e5-9142-5df6a83b9062\",\"order_by\":3,\"name\":\"Gökhan AKÇAKAVAK\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Aksaray\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Gökhan\",\"middleName\":\"\",\"lastName\":\"AKÇAKAVAK\",\"suffix\":\"\"},{\"id\":492368296,\"identity\":\"291d94b9-8542-4b1b-b073-a13de2833ce5\",\"order_by\":4,\"name\":\"Nevzat Emre ASLAN\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Bozok\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Nevzat\",\"middleName\":\"Emre\",\"lastName\":\"ASLAN\",\"suffix\":\"\"},{\"id\":492368297,\"identity\":\"21a37102-f867-468f-a2fd-8ef7989b5ab9\",\"order_by\":5,\"name\":\"Özhan KARATAŞ\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Sivas Cumhuriyet\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Özhan\",\"middleName\":\"\",\"lastName\":\"KARATAŞ\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2025-06-11 20:23:15\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-6874729/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-6874729/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":87929513,\"identity\":\"167b907c-91bb-4ccf-bc92-f15ae2798400\",\"added_by\":\"auto\",\"created_at\":\"2025-07-30 13:18:16\",\"extension\":\"jpeg\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":583734,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eMicroscopic evaluation of samples from different groups stained with Hematoxylin-Eosin\\u003cstrong\\u003e (H\\u0026amp;E). \\u003c/strong\\u003eA-B-C. Representative images of control groups (Group I, Group II, Group III) showing a score of 3 in the endometriosis grading system. D. Image of Group IV showing a score of 0. E. Image of Group V showing a score of 2. F. Image of Group V showing a score of 2. (asterisk; inflammatory cell infiltration)\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage1.jpeg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6874729/v1/9a45e830f47b6b1efa52274f.jpeg\"},{\"id\":87929201,\"identity\":\"402d7823-1dde-462b-8032-1227c0204ba4\",\"added_by\":\"auto\",\"created_at\":\"2025-07-30 13:10:16\",\"extension\":\"jpeg\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":814864,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eImmunohistochemical expression of α-SMA, VEGFA, IL-6, and TNF-α across groups (DAB staining). (A; Group I, B; Group IV, C; Group V, D; Group VI)\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage2.jpeg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6874729/v1/032786fbf6f4f5d189fc4f15.jpeg\"},{\"id\":89365393,\"identity\":\"28ab118e-0bd8-400d-8267-c2694f462a38\",\"added_by\":\"auto\",\"created_at\":\"2025-08-19 09:09:09\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":2265528,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6874729/v1/3d368183-585c-4d3a-849f-e7817e647b27.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"The Comparative Evaluation of the Therapeutic Effects of Autologous Cytokine-Rich Serum and Platelet-Rich Plasma in an Experimental Endometriosis Model\",\"fulltext\":[{\"header\":\"INTRODUCTION\",\"content\":\"\\u003cp\\u003eEndometriosis is an estrogen-dependent, chronic inflammatory disease characterized by the presence of endometrial glands and stroma in ectopic locations outside the uterus, most commonly in the ovaries, peritoneum, and the Douglas pouch. Affecting approximately 10% of women of reproductive age, endometriosis leads to symptoms such as chronic pelvic pain, dysmenorrhea, dyspareunia, dyschezia, and infertility, all of which significantly impair quality of life. Additionally, the disease often shows progressive behavior, and a significant proportion of cases experience recurrence over time (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003eAlthough the exact etiopathogenesis of endometriosis remains unclear, the most widely accepted hypothesis is Sampson\\u0026rsquo;s theory of retrograde menstruation. According to this theory, endometrial cells shed during menstruation reflux into the peritoneal cavity via the fallopian tubes, where they implant ectopically. However, since retrograde menstruation occurs in nearly all women, the fact that only certain individuals develop endometriosis suggests that additional factors\\u0026mdash;such as immune intolerance, cellular adhesion and invasion capacity, an inflammatory microenvironment, and genetic/epigenetic predispositions\\u0026mdash;may play key roles (\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003eAt the molecular level, endometriotic lesions are characterized by elevated expression of proinflammatory cytokines (e.g., TNF-α, IL-1β, IL-6), macrophage infiltration, increased angiogenesis (VEGF), and fibrogenesis (\\u003cspan additionalcitationids=\\\"CR6\\\" citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e). Under the influence of cytokines, growth factors, and reactive oxygen species, the microenvironment of ectopic endometrial tissue gains proliferative and invasive characteristics, which contribute to disease persistence and progression (\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003eCurrent treatment strategies for endometriosis primarily include surgical excision and hormonal therapies. However, these approaches have notable limitations. Hormonal treatments often produce menopausal side effects (such as osteoporosis and vasomotor symptoms), making long-term use poorly tolerated, while surgical interventions are invasive and frequently associated with high recurrence rates. Therefore, there is a growing need for more targeted, innovative therapeutic alternatives with minimal side effects that can address the underlying pathogenesis of the disease.\\u003c/p\\u003e\\u003cp\\u003eIn this context, regenerative medicine and biologic therapies have gained increasing attention. Platelet-Rich Plasma (PRP), an autologous product derived from whole blood and enriched with high concentrations of platelets, contains a variety of growth factors (PDGF, VEGF, EGF, TGF-β, IGF) and cytokines involved in wound healing, tissue regeneration, and modulation of inflammation. When applied locally, PRP promotes fibroblast proliferation, stimulates angiogenesis and extracellular matrix synthesis, and modulates immune responses. Currently, it is used therapeutically in various medical fields, including orthopedics, dermatology, urology, and gynecology (\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003eAnother promising biologic therapy developed in recent years is Autologous Cytokine-Rich Serum (ACRS), which is produced by incubating autologous blood under specific conditions for several hours, resulting in a serum enriched particularly with anti-inflammatory cytokines (IL-1ra, IL-4, IL-10). ACRS is notably rich in IL-1 receptor antagonist (IL-1ra), which plays a critical role in suppressing the inflammatory response (\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e). Its clinical efficacy has been demonstrated in chronic inflammatory conditions such as osteoarthritis, musculoskeletal disorders, and neuropathic pain (\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003eThe anti-inflammatory, antifibrotic, and regenerative properties of both PRP and ACRS align with the pathophysiological mechanisms of endometriosis (\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e). However, their potential effects in endometriosis, a complex and inflammation-driven disease, remain inadequately explored. Thus, investigating and comparing the therapeutic efficacy of PRP and ACRS in endometriosis from a molecular perspective is of considerable importance.\\u003c/p\\u003e\\u003cp\\u003eThe aim of this study was to comparatively evaluate the effects of intraovarian administration of PRP and ACRS on inflammation (TNF-α, IL-6), angiogenesis (VEGFA), and fibrosis (α-SMA) in an experimentally induced model of endometriosis. In this context, the study analyzed the potential of these two therapeutic agents to modulate the molecular pathogenesis of endometriosis and explored their viability as novel preclinical treatment options (\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e).\\u003c/p\\u003e\"},{\"header\":\"MATERIALS AND METHODS\",\"content\":\"\\u003cp\\u003e This study was conducted at the Erciyes University Experimental Research and Application Center (DEKAM) with the approval of the Erciyes University Local Animal Ethics Committee (HADYEK, Decision No: 24/023). All experimental procedures were carried out in accordance with international guidelines for the care and use of laboratory animals.\\u003c/p\\u003e\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eARRIVE Guidelines Compliance Statement:\\u003c/h2\\u003e\\u003cp\\u003eThis study was conducted and reported in accordance with the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines (\\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://arriveguidelines.org\\u003c/span\\u003e\\u003cspan address=\\\"https://arriveguidelines.org\\\" targettype=\\\"URL\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e). All procedures involving animals were reviewed and approved by the Erciyes University Animal Experiments Local Ethics Committee (HADYEK) on February 7, 2024 (Decision No: 24/023). Every effort was made to minimize animal suffering and the number of animals used.\\u003c/p\\u003e\\u003cp\\u003eFemale Wistar Albino rats weighing between 200\\u0026ndash;300 g and aged 16\\u0026ndash;24 weeks were used in the study. The animals were obtained from Erciyes University DEKAM. They were housed in disinfected cages in groups of 4\\u0026ndash;5 per cage, with free access to standard rat chow and water (ad libitum). The animals were maintained under controlled environmental conditions with a 12-hour light/dark cycle. All experimental procedures were performed at the same time of day to avoid circadian variations.\\u003c/p\\u003e\\u003c/div\\u003e\\n\\u003ch3\\u003eExperimental Groups\\u003c/h3\\u003e\\n\\u003cp\\u003eA total of 36 rats were randomly divided into six groups (n\\u0026thinsp;=\\u0026thinsp;6 per group) as follows:\\u003c/p\\u003e\\u003cp\\u003e\\u003cul\\u003e\\u003cli\\u003e\\u003cp\\u003e\\u003cb\\u003eGroup I (Control group)\\u003c/b\\u003e: No intervention was performed.\\u003c/p\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cp\\u003e\\u003cb\\u003eGroup II (PRP control group)\\u003c/b\\u003e: Treated with platelet-rich plasma (PRP) only.\\u003c/p\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cp\\u003e\\u003cb\\u003eGroup III (ACRS control group)\\u003c/b\\u003e: Treated with autologous cytokine-rich serum (ACRS) only.\\u003c/p\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cp\\u003e\\u003cb\\u003eGroup IV (Endometriosis\\u0026ndash;distilled water group)\\u003c/b\\u003e: Endometriosis was induced, and distilled water was administered.\\u003c/p\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cp\\u003e\\u003cb\\u003eGroup V (Endometriosis\\u0026ndash;PRP group)\\u003c/b\\u003e: Endometriosis was induced, and PRP treatment was administered.\\u003c/p\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cp\\u003e\\u003cb\\u003eGroup VI (Endometriosis\\u0026ndash;ACRS group)\\u003c/b\\u003e: Endometriosis was induced, and ACRS treatment was administered.\\u003c/p\\u003e\\u003c/li\\u003e\\u003c/ul\\u003e\\u003c/p\\u003e\\u003cp\\u003eAdditionally, six rats were used as blood donors for the preparation of PRP and ACRS.\\u003c/p\\u003e\\n\\u003ch3\\u003eEndometriosis Model\\u003c/h3\\u003e\\n\\u003cp\\u003eAn experimental endometriosis model was established using the technique described by Vernon and Wilson (\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e), which has been shown in subsequent studies to closely mimic human endometriosis (\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e). General anesthesia was induced with intraperitoneal administration of ketamine (60 mg/kg) and xylazine (10 mg/kg) (\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e). Following anesthesia, the abdominal area was shaved and disinfected with povidone-iodine. A midline laparotomy was performed, and the right uterine horn was sutured to the peritoneal wall using 4/0 PDS to allow for autotransplantation (\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e). After the procedure, the fascia and peritoneum were closed with 3/0 PDS sutures, and the skin was closed with 2/0 PGA. To allow for the formation of endometriotic lesions, animals were monitored for 4 weeks postoperatively (\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e).\\u003c/p\\u003e\\n\\u003ch3\\u003ePreparation Protocols for PRP and ACRS\\u003c/h3\\u003e\\n\\u003cp\\u003eFor PRP preparation, blood was collected from donor rats via intracardiac puncture under general anesthesia (\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e) and transferred into tubes containing acid-citrate-dextrose (ACD) solution (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e). The samples were centrifuged at 1000 rpm for 10 minutes. After centrifugation, three layers formed: red blood cells at the bottom, a \\\"buffy coat\\\" layer in the middle containing platelets, leukocytes, and a small amount of erythrocytes, and platelet-poor plasma at the top. The plasma fraction was carefully aspirated up to the interface layer using a pipette and transferred into a separate sterile tube (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e). Approximately 6 ml of PRP was obtained from 10 ml of whole blood (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e).\\u003c/p\\u003e\\n\\u003ch3\\u003ePreparation of ACRS\\u003c/h3\\u003e\\n\\u003cp\\u003eFor the preparation of Autologous Cytokine-Rich Serum (ACRS), intracardiac blood was collected from donor rats under general anesthesia and transferred into specialized kit tubes. The blood samples were incubated in a dedicated incubator for 3 hours, followed by centrifugation at 4000 rpm for 5 minutes (\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e). After centrifugation, the serum formed at the top was carefully aspirated using a pipette and transferred into another tube. Approximately 6 mL of ACRS was obtained from 10 mL of blood (\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cdiv id=\\\"Sec8\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eTreatment Protocols\\u003c/h2\\u003e\\u003cp\\u003eIn Groups II and III, the rats underwent laparotomy under general anesthesia (\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e), and a single dose of 0.5 mL of PRP or ACRS was administered directly into the right ovary via intraovarian injection (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e). This was followed by two additional intraperitoneal injections of 0.5 mL PRP or ACRS at one-week intervals (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003eIn Groups IV, V, and VI, after endometriosis model induction and a 4-week period for lesion development (\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e), a laparotomy was performed under general anesthesia (\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e). A single dose of 0.5 mL of distilled water (Group IV), PRP (Group V), or ACRS (Group VI) was administered intraovarianly to the right ovary (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e). Subsequently, two additional doses of 0.5 mL distilled water, PRP, or ACRS were administered intraperitoneally at one-week intervals (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003eAt the end of the study (Day 31 for the control groups and Day 45 for the endometriosis groups), all rats were sacrificed under anesthesia with xylazine (10 mg/kg) and ketamine (60 mg/kg) via cervical dislocation (\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e). The abdominal cavities were opened, and endometriotic lesions and relevant tissue samples were collected for histopathological and immunohistochemical analysis (11,12.14).\\u003c/p\\u003e\\u003c/div\\u003e\\n\\u003ch3\\u003eHistopathological and Immunohistochemical Analysis\\u003c/h3\\u003e\\n\\u003cp\\u003eUterine tissue samples collected post-necropsy were fixed in 10% neutral buffered formalin (\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e). Following fixation, tissues underwent routine histological processing and were embedded in paraffin blocks. Sections of 4\\u0026ndash;5 \\u0026micro;m thickness were cut from the paraffin blocks, stained with hematoxylin and eosin (H\\u0026amp;E), and examined under a light microscope (Olympus BX51, Tokyo, Japan) (\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR25\\\" class=\\\"CitationRef\\\"\\u003e25\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003eFor the histopathological evaluation, the endometriosis grading system previously described was employed (\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR26\\\" class=\\\"CitationRef\\\"\\u003e26\\u003c/span\\u003e). According to this system, tissue samples were semi-quantitatively scored by a blinded pathologist as follows:\\u003c/p\\u003e\\u003cp\\u003e\\u003cul\\u003e\\u003cli\\u003e\\u003cp\\u003e0: No epithelial lining\\u003c/p\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cp\\u003e1: Poorly preserved epithelium (epithelial cells present only occasionally)\\u003c/p\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cp\\u003e2: Moderately preserved epithelium with leukocyte infiltration\\u003c/p\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cp\\u003e3: Well-preserved epithelial layers\\u003c/p\\u003e\\u003c/li\\u003e\\u003c/ul\\u003e\\u003c/p\\u003e\\u003cp\\u003eFor immunohistochemical analysis, sections from paraffin blocks were subjected to deparaffinization and rehydration. Immunohistochemical staining was performed using a commercial kit (UltraVision Large Volume Detection System Anti-Polyvalent, HRP, TP-060-HL) according to the manufacturer\\u0026rsquo;s instructions (\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e). The following primary antibodies were used:\\u003c/p\\u003e\\u003cp\\u003e\\u003cul\\u003e\\u003cli\\u003e\\u003cp\\u003eα-SMA (alpha-smooth muscle actin, Affinity Biosciences, AF1032, dilution 1:200) (\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cp\\u003eTNF-α (Tumor necrosis factor-alpha, Santa Cruz Biotechnology, sc-133192, dilution 1:400) (\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cp\\u003eIL-6 (Interleukin-6, Affinity Biosciences, DF6087, dilution 1:400) (\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cp\\u003eVEGFA (Vascular Endothelial Growth Factor A, Affinity Biosciences, AF5131, dilution 1:200) (\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/li\\u003e\\u003c/ul\\u003e\\u003c/p\\u003e\\u003cp\\u003eDAB (3,3'-diaminobenzidine) was used as the chromogen, and counterstaining was performed with Mayer\\u0026rsquo;s hematoxylin (\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e). Immunohistochemical scoring was conducted semi-quantitatively by a blinded pathologist based on staining intensity and extent: 0 (none), 1 (mild), 2 (moderate), and 3 (strong) (\\u003cspan citationid=\\\"CR27\\\" class=\\\"CitationRef\\\"\\u003e27\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cdiv id=\\\"Sec10\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eStatistical Analysis\\u003c/h2\\u003e\\u003cp\\u003eStatistical analysis of data was performed using the nonparametric Kruskal\\u0026ndash;Wallis test. Pairwise comparisons between groups were conducted using the Mann\\u0026ndash;Whitney U test. A p-value\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05 was considered statistically significant. All analyses were performed using appropriate statistical software.\\u003c/p\\u003e\\u003c/div\\u003e\"},{\"header\":\"RESULTS\",\"content\":\"\\u003cp\\u003eHistopathological examination revealed that uterine tissues in the control groups (Groups I, II, and III) exhibited normal histological architecture (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e.A-B-C). In the endometriosis-induced groups (Groups IV, V, and VI), glandular epithelial hyperplasia, secretions within endometrial gland lumens, inflammatory cell infiltration in the stroma, and numerous macrophages with hemosiderin-laden cytoplasm were observed (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e.D-F). In the endometriosis-ACRS group (Group VI), the frequency and severity of lesions were found to be reduced compared to the endometriosis-distilled water group (Group IV).\\u003c/p\\u003e\\u003cp\\u003e\\u003c/p\\u003e\\u003cp\\u003eEndometriosis grading scores were lowest in Group IV compared to the control groups (Groups I, II, and III), and this difference was statistically significant. In Group VI, which received ACRS treatment, endometriosis scores were significantly increased compared to Group IV (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003e\\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e\\u003ccaption language=\\\"En\\\"\\u003e\\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e\\u003cdiv class=\\\"CaptionContent\\\"\\u003e\\u003cp\\u003eEndometriosis grading and immunohistochemical scores among groups\\u003c/p\\u003e\\u003cp\\u003e(Mean\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;SE).\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/caption\\u003e\\u003ccolgroup cols=\\\"7\\\"\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c6\\\" colnum=\\\"6\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c7\\\" colnum=\\\"7\\\"\\u003e\\u003c/div\\u003e\\u003cthead\\u003e\\u003ctr\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eGroup-I\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eGroup-II\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003eGroup-III\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003eGroup-IV\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003eGroup-V\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u003cp\\u003eGroup-VI\\u003c/p\\u003e\\u003c/th\\u003e\\u003c/tr\\u003e\\u003c/thead\\u003e\\u003ctbody\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eEndometriosis grading\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e3.00\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.00\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e2.83\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.17\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e2.83\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.17\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e1.33\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.21\\u003csup\\u003ec\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003e1.67\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.21\\u003csup\\u003ec\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u003cp\\u003e2.33\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.21\\u003csup\\u003eab\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eα-SMA\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e1.83\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.30\\u003csup\\u003eab\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e2.00\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.36\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e2.00\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.36\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e1.33\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.21\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003e1.50\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.22\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u003cp\\u003e2.33\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.21\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eVEGFA\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e1.67\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.33\\u003csup\\u003eab\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e1.83\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.40\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e1.83\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.30\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e1.17\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.17\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003e1.33\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.21\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u003cp\\u003e2.17\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.30\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eIL-6\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e0.17\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.17\\u003csup\\u003ec\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e0.33\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.21\\u003csup\\u003ec\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e0.50\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.22\\u003csup\\u003ec\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e2.50\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.22\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003e1.83\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.17\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u003cp\\u003e1.33\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.21\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eTNF- α\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e0.33\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.21\\u003csup\\u003ec\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e0.33\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.21\\u003csup\\u003ec\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e0.50\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.22\\u003csup\\u003ec\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e2.33\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.21\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003e1.67\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.21\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u003cp\\u003e1.17\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.17\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003c/tbody\\u003e\\u003c/colgroup\\u003e\\u003ctfoot\\u003e\\u003ctr\\u003e\\u003ctd colspan=\\\"7\\\"\\u003e\\u003csup\\u003ea\\u0026minus;d\\u003c/sup\\u003eLetters in the same row indicate statistically significant differences between groups (p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001).\\u003c/td\\u003e\\u003c/tr\\u003e\\u003c/tfoot\\u003e\\u003c/table\\u003e\\u003c/div\\u003e\\u003c/p\\u003e\\u003cp\\u003eImmunohistochemical staining (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e) showed that VEGFA and α-SMA expression scores were lowest in Group IV and highest in Group VI. ACRS treatment in Group VI significantly increased VEGFA and α-SMA immunoreactivity compared to Group IV, indicating that ACRS therapy enhances angiogenesis and myofibroblast activity.\\u003c/p\\u003e\\u003cp\\u003e\\u003c/p\\u003e\\u003cp\\u003eFor TNF-α and IL-6 immunostaining, the lowest scores were observed in the control groups (Groups I, II, and III), whereas the highest scores were detected in the endometriosis-distilled water group (Group IV). Both PRP (Group V) and ACRS (Group VI) treatments significantly reduced TNF-α and IL-6 expressions compared to Group IV. This reduction was more pronounced in the ACRS-treated group. These findings suggest that ACRS treatment may be more effective than PRP in suppressing the inflammatory response.\\u003c/p\\u003e\"},{\"header\":\"DISCUSSION\",\"content\":\"\\u003cp\\u003eEndometriosis is a complex, estrogen-dependent inflammatory disease that causes significant symptoms such as chronic pelvic pain, dysmenorrhea, and infertility in women, negatively affecting quality of life. The multifactorial etiology of the disease and its tendency to recur often lead to the inadequacy of current treatment approaches. Although surgical excision and hormonal therapies aim to suppress the disease, their long-term success rates are relatively low, and recurrent symptoms are frequently observed in many cases (\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e). In this context, regenerative medicine-based biological treatment approaches such as platelet-rich plasma (PRP) and autologous cytokine-rich serum (ACRS) have attracted attention for their potential in modulating inflammation and supporting tissue regeneration (\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e). In this study, the effects of ACRS and PRP treatments on an experimental endometriosis model were evaluated comparatively. Both treatments demonstrated therapeutic effects on the lesions; however, these effects appear to occur through different molecular mechanisms.\\u003c/p\\u003e\\u003cdiv id=\\\"Sec13\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eEffects on the Inflammatory Response\\u003c/h2\\u003e\\u003cp\\u003eIt is well-established that immune dysregulation and chronic inflammation play a central role in the pathogenesis of endometriosis (\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e). Particularly, elevated levels of pro-inflammatory cytokines such as TNF-α and IL-6 in peritoneal fluid and endometriotic lesions emphasize the importance of inflammation in disease progression (\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e). In our study, significantly increased levels of these cytokines were observed in the untreated group with induced endometriosis, confirming the pathophysiological validity of the model. Both ACRS and PRP treatments significantly reduced TNF-α and IL-6 expression levels, indicating that both biological agents have anti-inflammatory potential. However, the decrease was more pronounced in the ACRS-treated group, suggesting that ACRS may have a stronger anti-inflammatory effect. This could be attributed to the presence of potent anti-inflammatory cytokines in ACRS, such as IL-1 receptor antagonist (IL-1Ra), IL-4, and IL-10 (\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e). These findings suggest that ACRS may be a promising treatment option targeting the inflammatory component of endometriosis, potentially providing symptomatic relief.\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec14\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eEffects on Angiogenesis and Myofibroblast Activity\\u003c/h2\\u003e\\u003cp\\u003eThe persistence of endometriotic lesions is not only associated with inflammation but also with processes such as angiogenesis and fibrosis (\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e). VEGFA has been identified as a key factor responsible for the vascularization of endometriotic foci. α-SMA is an indicator of myofibroblast activity and fibrotic tissue remodeling, and it may play a role in the chronic persistence of lesions (\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e). In our study, ACRS treatment significantly increased both VEGFA and α-SMA expression. This indicates that ACRS not only suppresses inflammation but may also stimulate tissue regeneration and vascular remodeling. However, it should be noted that this increase could facilitate structural stability of the lesions rather than regression, potentially increasing the risk of recurrence in the long term. These findings underscore the need for further experimental studies to evaluate the potential proliferative effects of ACRS before clinical application. On the other hand, PRP treatment induced more limited changes in VEGFA and α-SMA expression levels. This suggests that although PRP is rich in growth factors, its cytokine composition may differ from that of ACRS and possibly be more balanced (\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e). This property of PRP may lead to a more controlled therapeutic response by moderately supporting both inflammation modulation and tissue remodeling.\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec15\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eClinical Implications and Evaluation of Treatment Options\\u003c/h2\\u003e\\u003cp\\u003eHistopathological scoring of endometriosis revealed significant differences among treatment groups. Particularly, the higher scores observed in the ACRS group suggest better preservation of lesion structures. This may point to ACRS's tissue-supportive effects; however, it should also be considered that such protective effects might hinder lesion regression.\\u003c/p\\u003e\\u003cp\\u003eFrom a clinical perspective, ACRS may contribute to symptom relief by suppressing inflammatory processes, while PRP, due to its more limited effect on angiogenesis and balanced cytokine profile, might present a safer and more conservative therapeutic option that is less likely to promote lesion persistence (\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e). Based on these results, PRP could be considered a more balanced and safer biological agent for endometriosis treatment, whereas ACRS may be preferable in cases where inflammation suppression is a primary goal. Nonetheless, these suggestions require further support through advanced preclinical and clinical studies on human tissues before being integrated into clinical practice.\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec16\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eStudy Limitations and Future Perspectives\\u003c/h2\\u003e\\u003cp\\u003eThe limitations of this study include the small sample size, the focus on only specific biomarkers, and the lack of evaluation of the long-term effects of the treatments. Additionally, the experimental model used in this study only partially reflects human pathophysiology, limiting the generalizability of the findings (\\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e). Future research should compare different doses and administration regimens of ACRS and PRP and evaluate broader inflammatory, fibrotic, and angiogenic responses at the molecular level. Furthermore, investigating the effects of these treatments on fertility, endometrial receptivity, and oocyte quality is essential for potential clinical translation.\\u003c/p\\u003e\\u003c/div\\u003e\"},{\"header\":\"CONCLUSION\",\"content\":\"\\u003cp\\u003eThis experimental study is one of the first in the literature to comparatively investigate the therapeutic effects of autologous cytokine-rich serum (ACRS) and platelet-rich plasma (PRP) on endometriosis. Our findings reveal that both biological products exert anti-inflammatory effects on endometriotic lesions; however, the underlying molecular mechanisms differ between the two treatments.\\u003c/p\\u003e\\u003cp\\u003eIn particular, ACRS treatment showed a stronger suppressive effect on the expression of proinflammatory cytokines (TNF-α and IL-6) compared to PRP. Additionally, the increased levels of VEGFA and α-SMA following ACRS application suggest that angiogenesis and myofibroblast activity are more prominently induced by ACRS. This indicates that ACRS not only suppresses inflammation but may also remodel the lesion microenvironment through its biological activity. Similarly, PRP treatment reduced the inflammatory response, though its effects on angiogenesis and fibrotic activity were less pronounced than those of ACRS.\\u003c/p\\u003e\\u003cp\\u003eThis suggests that PRP may exert a more limited but targeted anti-inflammatory effect. In contrast, ACRS appears to offer a more complex mechanism of action by influencing immunomodulatory, regenerative, and cell signaling pathways. In this context, both treatment approaches offer promising potential as alternative biological therapies for the management of endometriosis. However, to fully understand the effects of these biological products on endometriosis, it is essential to further elucidate their mechanisms of action at the cellular and molecular levels, evaluate their long-term outcomes, and identify any possible adverse effects. Furthermore, future translational and clinical studies should focus on whether the combination of PRP or ACRS with standard hormonal or surgical treatments can create a synergistic effect and offer therapeutic benefits in cases of resistant or recurrent endometriosis.\\u003c/p\\u003e\\u003cdiv id=\\\"Sec18\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eKey Findings:\\u003c/h2\\u003e\\u003cp\\u003e\\u003cul\\u003e\\u003cli\\u003e\\u003cp\\u003eBoth ACRS and PRP treatments reduced the inflammatory response in an experimental endometriosis model.\\u003c/p\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cp\\u003eACRS more effectively suppressed TNF-α and IL-6 expression compared to PRP, while also increasing VEGFA and α-SMA expression levels.\\u003c/p\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cp\\u003eThese findings suggest that ACRS plays an active role not only in inflammation control but also in angiogenesis and stromal remodeling processes.\\u003c/p\\u003e\\u003c/li\\u003e\\u003c/ul\\u003e\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec19\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eClinical Applications:\\u003c/h2\\u003e\\u003cp\\u003e\\u003cul\\u003e\\u003cli\\u003e\\u003cp\\u003eThe data suggest that ACRS and PRP could be considered complementary or alternative treatment options, especially in cases resistant to conventional therapies or in recurrent endometriosis.\\u003c/p\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cp\\u003eACRS, with its potential to modulate immune response and support tissue regeneration, may hold a significant place in future personalized treatment strategies for endometriosis.\\u003c/p\\u003e\\u003c/li\\u003e\\u003c/ul\\u003e\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec20\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eFuture Research:\\u003c/h2\\u003e\\u003cp\\u003e\\u003cul\\u003e\\u003cli\\u003e\\u003cp\\u003eThe long-term effects of ACRS and PRP, as well as optimal dosages and application frequencies, need to be established.\\u003c/p\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cp\\u003eEvaluating the efficacy of these biological therapies in combination with hormonal treatments or surgical interventions may be crucial in developing next-generation endometriosis treatment protocols.\\u003c/p\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cp\\u003eIt is recommended that future studies explore their molecular effects, particularly on the TGF-β pathway, macrophage polarization, ECM remodeling, and epithelial-mesenchymal transition (EMT).\\u003c/p\\u003e\\u003c/li\\u003e\\u003c/ul\\u003e\\u003c/p\\u003e\\u003c/div\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eAuthors contributions:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eEK conducted the experimental animal studies and drafted the manuscript. EK, HE and NEA performed the experimental design. NEA and HE participated in the review and editing of the manuscript. EK, HE and ME conceived the study, participated in its design and coordination, and assisted in the preparation of the manuscript. GA performed histopathology and statistical analyses. GA and OK performed immunohistochemical staining and analysis. All authors read and approved the final version of the manuscript.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding Statement:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNo funding was received for this study. The authors funded the study themselves.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgement:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors thank laboratory technicians for their assistance with histological preparations and animal care staff for their support.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eEthical Statement:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe present study was conducted at the Erciyes University Experimental Research\\u003c/p\\u003e\\n\\u003cp\\u003eApplication and Research Center (DEKAM) with the approval of the Erciyes\\u003c/p\\u003e\\n\\u003cp\\u003eUniversity Animal Experiments Local Ethics Committee (HADYEK, Decision no:\\u003c/p\\u003e\\n\\u003cp\\u003e24/023).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eDeclaration of conflicting interests:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eData avalibility:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAll the data are included in the manuscript.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eDing, Y., Bian, X., Jiang, Y., Luo, L. \\u0026amp; Li, X. The therapeutic effect of platelet-rich plasma in the treatment of endometriosis: A review of the literature. \\u003cem\\u003eGynecol. Endocrinol.\\u003c/em\\u003e \\u003cb\\u003e39\\u003c/b\\u003e (4), 347\\u0026ndash;353. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1080/09513590.2022.2159544\\u003c/span\\u003e\\u003cspan address=\\\"10.1080/09513590.2022.2159544\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (2023).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003ePajot, C., De Smedt, J., Langlois, M., Donnez, J. \\u0026amp; Dolmans, M. M. Regenerative medicine strategies for the treatment of endometriosis: A systematic review. \\u003cem\\u003eReprod. Sci.\\u003c/em\\u003e \\u003cb\\u003e28\\u003c/b\\u003e (8), 2077\\u0026ndash;2090. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1007/s43032-020-00369-4\\u003c/span\\u003e\\u003cspan address=\\\"10.1007/s43032-020-00369-4\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (2021).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eHuang, X., Liu, J., Wang, T., Wang, X. \\u0026amp; Li, J. Platelet-rich plasma modulates the inflammatory response and promotes tissue regeneration: A potential therapy for endometriosis? \\u003cem\\u003eReprod. Sci.\\u003c/em\\u003e \\u003cb\\u003e28\\u003c/b\\u003e (5), 1369\\u0026ndash;1376. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1007/s43032-020-00429-9\\u003c/span\\u003e\\u003cspan address=\\\"10.1007/s43032-020-00429-9\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (2021).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003evan Buul, G. M. et al. Platelet-rich plasma releasate inhibits inflammatory processes in osteoarthritic chondrocytes. \\u003cem\\u003eAm. J. Sports Med.\\u003c/em\\u003e \\u003cb\\u003e39\\u003c/b\\u003e (11), 2362\\u0026ndash;2370. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1177/0363546511419278\\u003c/span\\u003e\\u003cspan address=\\\"10.1177/0363546511419278\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (2011).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eWehling, P. et al. Autologous conditioned serum in the treatment of orthopedic diseases: The orthokine therapy. \\u003cem\\u003eBioDrugs\\u003c/em\\u003e \\u003cb\\u003e21\\u003c/b\\u003e (5), 323\\u0026ndash;332. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.2165/00063030-200721050-00003\\u003c/span\\u003e\\u003cspan address=\\\"10.2165/00063030-200721050-00003\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (2007).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eWehling, P. et al. Clinical responses to cytokine inhibition in arthritis and osteoarthritis. \\u003cem\\u003eBioDrugs\\u003c/em\\u003e \\u003cb\\u003e21\\u003c/b\\u003e (3), 165\\u0026ndash;174. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.2165/00063030-200721030-00002\\u003c/span\\u003e\\u003cspan address=\\\"10.2165/00063030-200721030-00002\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (2007).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eZhu, J. et al. The role of cytokines and growth factors in endometriosis: A review. \\u003cem\\u003eReprod. Sci.\\u003c/em\\u003e \\u003cb\\u003e25\\u003c/b\\u003e (4), 497\\u0026ndash;508. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1177/1933719117710340\\u003c/span\\u003e\\u003cspan address=\\\"10.1177/1933719117710340\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (2018).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eHsu, A. L., Khachikyan, I. \\u0026amp; Stratton, P. Inflammation and endometriosis. \\u003cem\\u003eSemin Reprod. Med.\\u003c/em\\u003e \\u003cb\\u003e33\\u003c/b\\u003e (5), 316\\u0026ndash;325. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1055/s-0035-1557836\\u003c/span\\u003e\\u003cspan address=\\\"10.1055/s-0035-1557836\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (2015).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eBulun, S. E. \\u0026amp; Endometriosis \\u003cem\\u003eN Engl. J. Med.\\u003c/em\\u003e ;\\u003cb\\u003e360\\u003c/b\\u003e(3):268\\u0026ndash;279. doi:\\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1056/NEJMra0804690\\u003c/span\\u003e\\u003cspan address=\\\"10.1056/NEJMra0804690\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (2009).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eVercellini, P., Vigan\\u0026ograve;, P., Somigliana, E., Fedele, L. \\u0026amp; Endometriosis Pathogenesis and clinical impact. \\u003cem\\u003eHum. Reprod. Update\\u003c/em\\u003e. \\u003cb\\u003e20\\u003c/b\\u003e (6), 760\\u0026ndash;772. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1093/humupd/dmu025\\u003c/span\\u003e\\u003cspan address=\\\"10.1093/humupd/dmu025\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (2014).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eVernon, M. W. \\u0026amp; Wilson, E. A. Studies on the surgical induction of endometriosis in the rat. \\u003cem\\u003eFertil. Steril.\\u003c/em\\u003e \\u003cb\\u003e44\\u003c/b\\u003e (5), 684\\u0026ndash;694. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1016/s0015-0282(16)49063-4\\u003c/span\\u003e\\u003cspan address=\\\"10.1016/s0015-0282(16)49063-4\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (1985).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eGr\\u0026uuml;mmer, R. Animal models in endometriosis research. \\u003cem\\u003eHum. Reprod. Update\\u003c/em\\u003e. \\u003cb\\u003e12\\u003c/b\\u003e (5), 641\\u0026ndash;649. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1093/humupd/dml024\\u003c/span\\u003e\\u003cspan address=\\\"10.1093/humupd/dml024\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (2006).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eCakmak, H. \\u0026amp; Taylor, H. S. Implantation failure: Molecular mechanisms and clinical treatment. \\u003cem\\u003eHum. Reprod. Update\\u003c/em\\u003e. \\u003cb\\u003e17\\u003c/b\\u003e (2), 242\\u0026ndash;253. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1093/humupd/dmq037\\u003c/span\\u003e\\u003cspan address=\\\"10.1093/humupd/dmq037\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (2011).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eZindler, T. et al. Animal models of endometriosis and their application for novel drug development. \\u003cem\\u003eJ. Endometr. Pelvic Pain Disord\\u003c/em\\u003e. \\u003cb\\u003e11\\u003c/b\\u003e (1), 1\\u0026ndash;8. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1177/2284026519831148\\u003c/span\\u003e\\u003cspan address=\\\"10.1177/2284026519831148\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (2019).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eGiudice, L. C., Kao, L. C. \\u0026amp; Endometriosis \\u003cem\\u003eLancet\\u003c/em\\u003e ;\\u003cb\\u003e364\\u003c/b\\u003e(9447):1789\\u0026ndash;1799. doi:\\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1016/S0140-6736(04)17403-5\\u003c/span\\u003e\\u003cspan address=\\\"10.1016/S0140-6736(04)17403-5\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (2004).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eMarx, R. E. Platelet-rich plasma: evidence to support its use. \\u003cem\\u003eJ. Oral Maxillofac. Surg.\\u003c/em\\u003e \\u003cb\\u003e62\\u003c/b\\u003e (4), 489\\u0026ndash;496. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1016/j.joms.2003.12.003\\u003c/span\\u003e\\u003cspan address=\\\"10.1016/j.joms.2003.12.003\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (2004).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eLebovic, D. I., Mueller, M. D. \\u0026amp; Taylor, R. N. Immunobiology of endometriosis. \\u003cem\\u003eFertil. Steril.\\u003c/em\\u003e \\u003cb\\u003e75\\u003c/b\\u003e (1), 1\\u0026ndash;10. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1016/S0015-0282(00)01656-0\\u003c/span\\u003e\\u003cspan address=\\\"10.1016/S0015-0282(00)01656-0\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (2001).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eGazvani, R. \\u0026amp; Templeton, A. Peritoneal environment, cytokines and angiogenesis in the pathophysiology of endometriosis. \\u003cem\\u003eReproduction\\u003c/em\\u003e \\u003cb\\u003e123\\u003c/b\\u003e (2), 217\\u0026ndash;226. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1530/rep.0.1230217\\u003c/span\\u003e\\u003cspan address=\\\"10.1530/rep.0.1230217\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (2002).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eAndrade, P. Z., dos Santos, F., da Silva, C. L. \\u0026amp; Cabral, J. M. Mesenchymal stem cell therapy for inflammatory diseases: mechanisms, challenges, and opportunities. \\u003cem\\u003eCell. Mol. Life Sci.\\u003c/em\\u003e \\u003cb\\u003e72\\u003c/b\\u003e (8), 1403\\u0026ndash;1420. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1007/s00018-014-1792-1\\u003c/span\\u003e\\u003cspan address=\\\"10.1007/s00018-014-1792-1\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (2015).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eDonnez, J., Smoes, P., Gillerot, S., Casanas-Roux, F. \\u0026amp; Nisolle, M. Vascular endothelial growth factor (VEGF) in endometriosis. \\u003cem\\u003eHum. Reprod.\\u003c/em\\u003e \\u003cb\\u003e13\\u003c/b\\u003e (6), 1686\\u0026ndash;1690. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1093/humrep/13.6.1686\\u003c/span\\u003e\\u003cspan address=\\\"10.1093/humrep/13.6.1686\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (1998).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eMeuleman, C., Tomassetti, C. \\u0026amp; D'Hooghe, T. Clinical outcome after CO2 laser laparoscopy in patients with minimal to moderate endometriosis. \\u003cem\\u003eFertil. Steril.\\u003c/em\\u003e \\u003cb\\u003e96\\u003c/b\\u003e (4), 912\\u0026ndash;916. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1016/j.fertnstert.2011.07.1102\\u003c/span\\u003e\\u003cspan address=\\\"10.1016/j.fertnstert.2011.07.1102\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (2011).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eAnitua, E., S\\u0026aacute;nchez, M., Orive, G. \\u0026amp; And\\u0026iacute;a, I. The potential impact of the preparation rich in growth factors (PRGF) in different medical fields. \\u003cem\\u003eBiomaterials\\u003c/em\\u003e \\u003cb\\u003e28\\u003c/b\\u003e (31), 4551\\u0026ndash;4560. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1016/j.biomaterials.2007.06.037\\u003c/span\\u003e\\u003cspan address=\\\"10.1016/j.biomaterials.2007.06.037\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (2007).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eChang, Y., Chen, Y., Wu, J. \\u0026amp; Chen, S. Platelet-rich plasma for treating endometriosis: an in vivo animal study. \\u003cem\\u003eTaiwan. J. Obstet. Gynecol.\\u003c/em\\u003e \\u003cb\\u003e57\\u003c/b\\u003e (4), 541\\u0026ndash;545. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1016/j.tjog.2018.06.006\\u003c/span\\u003e\\u003cspan address=\\\"10.1016/j.tjog.2018.06.006\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (2018).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eBorghese, B. et al. Research models of endometriosis. \\u003cem\\u003eInt. J. Dev. Biol.\\u003c/em\\u003e \\u003cb\\u003e62\\u003c/b\\u003e (1-2-3), 159\\u0026ndash;169. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1387/ijdb.170247fb\\u003c/span\\u003e\\u003cspan address=\\\"10.1387/ijdb.170247fb\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e (2018).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eKazak, F. et al. Proanthocyanidin alleviates testicular torsion/detorsion-induced ischemia/reperfusion injury in rats. \\u003cem\\u003eTissue Cell.\\u003c/em\\u003e \\u003cb\\u003e89\\u003c/b\\u003e, 102459 (2024).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eKeenan, J. A. et al. Regression of endometrial explants in a rat model of endometriosis treated with the imm\\u0026uuml;ne modulators loxoribine and levamisole. \\u003cem\\u003eFertil. Steril.\\u003c/em\\u003e \\u003cb\\u003e72\\u003c/b\\u003e (1), 135\\u0026ndash;141 (1999).\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eAkcakavak, G., Kazak, F. \\u0026amp; Yilmaz Deveci, M. Z. Eucalyptol Protects against Cisplatin-Induced Liver Injury in Rats. \\u003cem\\u003eBiology Bull.\\u003c/em\\u003e \\u003cb\\u003e50\\u003c/b\\u003e (5), 987\\u0026ndash;994 (2023).\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Endometriosis, Autologous Cytokine-Rich Serum (ACRS), Platelet-Rich Plasma (PRP), Inflammation, Angiogenesis, TNF-α, IL-6, VEGFA, α-SMA, rat\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-6874729/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-6874729/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003ePurpose:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis study aimed to comparatively evaluate the therapeutic effects of Autologous Cytokine-Rich Serum (ACRS) and Platelet-Rich Plasma (PRP) in a rat model of endometriosis, with a focus on inflammation, angiogenesis, and myofibroblast activity.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMethods:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eA total of 36 adult female Wistar Albino rats were randomly assigned to six groups: healthy control, ACRS-only, PRP-only, endometriosis (EM), EM + ACRS, and EM + PRP. Endometriosis was surgically induced in the relevant groups. ACRS and PRP were prepared from the animals' autologous blood and administered intraabdominally. After treatment, endometriotic implants were excised for histopathological scoring and immunohistochemical analysis targeting TNF-α, IL-6 (inflammation), VEGFA (angiogenesis), and α-SMA (myofibroblast activity).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResults:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eHistopathological scores significantly decreased in both EM + ACRS and EM + PRP groups compared to the EM group. ACRS demonstrated superior anti-inflammatory effects, with greater reductions in TNF-α and IL-6 expression than PRP. However, ACRS-treated tissues showed higher VEGFA and α-SMA expression, suggesting enhanced angiogenic and fibrotic responses relative to PRP.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusions:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eBoth ACRS and PRP exerted therapeutic effects in experimental endometriosis. ACRS was more effective in reducing inflammation but showed distinct effects on angiogenesis and fibrosis compared to PRP. These findings support the potential of ACRS as a novel therapeutic option, warranting further clinical investigation.\\u003c/p\\u003e\",\"manuscriptTitle\":\"The Comparative Evaluation of the Therapeutic Effects of Autologous Cytokine-Rich Serum and Platelet-Rich Plasma in an Experimental Endometriosis Model\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-07-30 13:10:11\",\"doi\":\"10.21203/rs.3.rs-6874729/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"9afb7498-44dc-42e1-bd3a-6fffd9950675\",\"owner\":[],\"postedDate\":\"July 30th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[{\"id\":52276265,\"name\":\"Biological sciences/Biological techniques\"},{\"id\":52276266,\"name\":\"Biological sciences/Immunology\"},{\"id\":52276267,\"name\":\"Biological sciences/Molecular biology\"},{\"id\":52276268,\"name\":\"Health sciences/Diseases\"},{\"id\":52276269,\"name\":\"Health sciences/Medical research\"},{\"id\":52276270,\"name\":\"Health sciences/Pathogenesis\"}],\"tags\":[],\"updatedAt\":\"2025-08-19T09:08:46+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2025-07-30 13:10:11\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-6874729\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-6874729\",\"identity\":\"rs-6874729\",\"version\":[\"v1\"]},\"buildId\":\"WvIrzKhiLBfengagbw6Ux\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC0","license_restricted":false}