{"paper_id":"22259d04-c921-46cd-bb51-14ad8a86c2ad","body_text":"© 2026 THE KOREAN SOCIETY FOR REPRODUCTIVE MEDICINE www.eCERM.org 1\nThis is an Open Access article distributed under the terms of the Creative Commons Attribu-\ntion Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits \nunrestricted non-commercial use, distribution, and reproduction in any medium, provided the \noriginal work is properly cited.\nStandardized method to develop an endometriosis \nmodel in Sprague–Dawley rats: A step-by-step \ndescription\nHerbert Situmorang\nDepartment of Obstetrics and Gynecology, Dr. Cipto Mangunkusumo National Referral Hospital, Faculty of Medicine, University of Indonesia, Jakarta, \nIndonesia\nORIGINAL ARTICLE\nhttps://doi.org/10.5653/cerm.2025.08690\npISSN 2233-8233 · eISSN 2233-8241\nClin Exp Reprod Med [Epub ahead of print]\nReceived: September 18, 2025 ∙ Revised: December 1, 2025 ∙ Accepted: February \n23, 2026\nCorresponding author: Herbert Situmorang\nDepartment of Obstetrics and Gynecology, Dr. Cipto Mangunkusumo National \nReferral Hospital, Faculty of Medicine, University of Indonesia, Jl. Salemba Raya \nNo. 6, Central Jakarta, Jakarta Capital Special Region, Indonesia\nTel: +62-813-8310-0567 E-mail: datadrherbert@gmail.com\nObjective:  To establish a standardized and reproducible rat model of endometriosis by refining the classic Vivian technique, with the aim of \nminimizing methodological variability and replicating key features of human disease.\nMethods:  Sixty female Sprague–Dawley rats (6 weeks old) were evaluated for estrous-cycle phase using vaginal cytology, and only animals \nin proestrus or estrus were selected. Under ketamine–xylazine anesthesia, a 1-cm segment of the uterine horn was excised, opened longitu-\ndinally, and sutured to the peritoneal wall with the endometrial surface facing the peritoneum. Protocol refinements included strict graft ori-\nentation, fixation with four interrupted sutures, and perioperative ceftriaxone prophylaxis. A second laparotomy was performed one month \nlater to assess lesion development, followed by histological confirmation.\nResults:  All animals (100%) developed macroscopically visible lesions. These lesions presented as cystic, fluid-filled masses with hyperemic \nsurfaces and neovascularization; adhesions to the bowel or omentum were also observed. Lesion size was quantified using digital imaging \nsoftware. Histological analysis confirmed the presence of endometrial-like tissue composed of cuboidal epithelium, glandular structures, and \nstromal elements. No perioperative mortality occurred.\nConclusion:  This standardized rat model reliably reproduces hallmark features of human endometriosis, including angiogenesis and adhe-\nsion formation. The protocol refinements address common sources of variability in rodent models and provide a stepwise, reproducible \nframework for mechanistic investigation and preclinical evaluation of novel therapies.\nKeywords: Adhesion; Angiogenesis; Animal model; Endometriosis; Experimental surgery; Histology; Homologous transplantation; Preclini-\ncal research; Reproducibility; Sprague–Dawley rat\nIntroduction\nEndometriosis is a chronic, estrogen-dependent disorder charac-\nterized by the presence of functional endometrial glands and stroma \noutside the uterine cavity. Ectopic lesions most commonly occur on \nthe ovaries, pelvic peritoneum, and uterosacral ligaments, although \nextrapelvic manifestations—such as involvement of the diaphragm \nor abdominal wall—have also been reported [1,2]. The condition af-\nfects an estimated 10% of women of reproductive age and is partic-\nularly prevalent among those with infertility, in whom rates may \nreach 30% to 50%, and among those with chronic pelvic pain, where \nprevalence may be as high as 70% to 80% [1,3]. Beyond its clinical \nmanifestations, endometriosis imposes substantial psychological \nand socioeconomic burdens, underscoring its importance as a major \npublic health concern.\nDespite decades of investigation, the pathogenesis of endometri-\nosis remains incompletely understood. Several theories have been \nproposed to explain the ectopic implantation and persistence of en-\ndometrial tissue. Sampson’s theory of retrograde menstruation re-\n\nadapted the Jones procedure in Wistar rats using a full-thickness \nuterine flap sutured to the abdominal wall, improving graft handling \nand lesion reproducibility. Collectively, these foundational models \nestablished the key methodological principles—autologous trans-\nplantation, stable tissue fixation, and hormonal responsiveness—\nthat continue to underpin contemporary induction techniques. Nev-\nertheless, variability persists in implantation success, tissue orienta-\ntion, suture configuration, infection control, estrous-cycle timing, \nand postoperative outcomes, with reported success rates ranging \nfrom 60% to 80%. Inconsistent graft adherence remains a significant \nlimitation, often leading to epithelial loss or incomplete lesion estab-\nlishment.\nIn the absence of a rigorously standardized rodent model with \nconsistently reproducible results, a methodological gap persists that \nlimits comparability across studies. The present study addresses \nthese shortcomings by refining the Vivian technique through strict \nestrous-phase synchronization, verified endometrial orientation, \nfour-point graft fixation, and prophylactic antibiotic administration. \nThese modifications are intended to reduce interoperator variability, \nenhance reproducibility, and provide a clearly defined standardized \nprotocol suitable for mechanistic and translational research.\nMethods\n1. Laboratory animals and ethical approval statement\nThe experiment was conducted between December 2019 and \nMay 2020 at the Animal Research Facility (ARF), Indonesian Medical \nEducation and Research Institute (IMERI), Faculty of Medicine, Uni-\nversitas Indonesia. The study was approved by the Ethics Committee \nof the Faculty of Medicine, Universitas Indonesia (approval no. KET-\n227/UN2.F1/ETIK/PPM.00.02/2020, issued February 24, 2020). All \nprocedures were performed in compliance with national regulations \nand international standards for the care and use of laboratory ani-\nmals. Sixty 6-week-old female Sprague–Dawley rats (Rattus norvegi-\ncus) were used for model induction. Animals were housed at the ARF , \nIMERI, Faculty of Medicine, Universitas Indonesia, in groups of five \nper cage under controlled temperature and humidity and a 12-hour \nlight/dark cycle, with free access to standard chow and water.\n2. Estrous-cycle determination\nEstrous cyclicity was assessed to ensure hormonal synchronization \nbefore surgery. Vaginal smears were obtained by gently inserting ei-\nther a plastic pipette containing 10 μL of sterile 0.9% sodium chlo-\nride or a saline-moistened cotton swab into the vaginal canal. Secre-\ntions were transferred to glass slides, fixed in 90% ethanol, and \nstained with Giemsa. Slides were examined using a standard light \nmicroscope. Estrous phases were classified as proestrus, estrus, \nmains the most widely cited; however, alternative hypotheses—in-\ncluding coelomic metaplasia and Müllerian remnant theories—also \nretain relevance [4,5]. These mechanisms are increasingly viewed not \nas mutually exclusive but as interconnected processes involving im-\nmune dysfunction, hormonal dysregulation, angiogenesis, and ge-\nnetic susceptibility that collectively drive lesion establishment and \npersistence [4,5]. This multifactorial complexity has hindered the de-\nvelopment of definitive diagnostic strategies and targeted therapies.\nClinically, endometriosis presents heterogeneously. Although \nsome women remain asymptomatic, many experience cyclic pelvic \npain, dysmenorrhea, dyspareunia, dyschezia, or urinary pain. Nota-\nbly, symptom severity does not consistently correlate with disease \nstage or depth of invasion [1]. Infertility, often resulting from pelvic \nadhesions and distorted pelvic anatomy, further highlights the pro-\nfound reproductive consequences of the disease [2]. Laparoscopy \nwith histopathological confirmation remains the diagnostic gold \nstandard, and current treatment strategies include hormonal sup-\npression, surgical excision, or a combination of both. However, none \nof these approaches guarantees long-term remission, and recurrence \nremains common.\nThe limitations of current diagnostic and therapeutic options un-\nderscore the need for reliable experimental models of endometriosis \nto elucidate disease mechanisms and facilitate therapeutic develop-\nment. Because spontaneous endometriosis occurs almost exclusively \nin nonhuman primates—models limited by ethical and financial \nconstraints—rodents have become indispensable in preclinical re-\nsearch. Among these species, the Sprague–Dawley rat is particularly \nadvantageous because of its predictable estrous cycles, ease of han-\ndling, and ability to generate reproducible lesions through surgical \ninduction [6]. However, unlike menstruating species, rats do not un-\ndergo cyclic endometrial shedding, limiting replication of Sampson’s \nretrograde menstruation theory. Consequently, surgically induced \nhomologous models remain the primary experimental approach in \nrats [7].\nThe earliest systematic rat model of endometriosis was described \nby Jones [8], who introduced a homologous autotransplantation \ntechnique in Sprague–Dawley rats. Their method involved excising a \nuterine horn segment, separating the myometrium from the endo-\nmetrium, and transplanting a standardized 5×5 mm endometrial \nfragment onto the peritoneal wall with the epithelial surface facing \nthe cavity. The graft was secured at four corners, and viability was as-\nsessed 3 weeks later [8]. Building on this approach, Vernon and Wil-\nson [ 9] compared three induction strategies—sutured uterine \nsquares, intraperitoneal luminal lavage, and dispersed endometrial \nscrapings—and demonstrated that only sutured autotransplants \nyielded viable, cystic lesions, thereby establishing surgical implanta-\ntion as the most reliable method. do Amaral et al. [10] subsequently \nhttps://doi.org/10.5653/cerm.2025.086902\nClin Exp Reprod Med [Epub ahead of print]\n\nmetestrus, or diestrus based on the relative proportions of epithelial \ncells and leukocytes (Figure 1) [11]. Cycles were considered normal \nwhen they repeated every 4–7 days. Only animals in proestrus or es-\ntrus underwent surgical induction to maximize implantation success.\n3. Induction of endometriosis\nAnesthesia was induced with intramuscular ketamine hydrochlo-\nride (90 mg/kg) and xylazine (10 mg/kg). Prior to surgery, animals \nwere weighed to calculate anesthetic dosage. After induction, the \nabdominal wall hair was removed using clippers, and rats were posi-\ntioned supine on a surgical board with limbs abducted. Routine \nasepsis and antisepsis were performed.\nA 4-cm midline incision was made below the umbilicus to expose \nthe peritoneal cavity. The bicornuate uterus was identified (Figure 2), \nand a 1-cm segment of uterine horn was excised after securing he-\nmostasis by proximal and distal ligation with 3–0 silk sutures. The ex-\ncised segment was opened longitudinally to expose the endometrial \nsurface (Figure 3). The flap of uterine tissue was prepared and su-\ntured to the anterior peritoneal wall of the right lower quadrant, ap-\nproximately 2 cm from the abdominal incision, with the endometrial \nside facing the peritoneum. Fixation was achieved using four inter-\nrupted 6–0 nylon sutures (Figure 4).\nAfter confirming hemostasis, the abdominal wall was closed with \n4–0 chromic catgut in one layer, and the skin was closed with 4–0 \nsilk sutures. Rats were returned to their cages after recovery from an-\nesthesia. Prophylactic antibiotic treatment was administered as in-\nFigure 1\nFigure 1.  Estrous cycle in rats. (A) Diestrus: Predominance of \nleukocytes with few or no epithelial cells. (B) Proestrus: Decreased \nleukocytes with increasing epithelial cells. (C) Estrus: Field composed \nentirely of epithelial cells, with no leukocytes observed. (D) \nMetestrus: Postestrus phase characterized by declining epithelial \ncells with a concomitant increase in leukocytes. Original micrographs \nreproduced from Zenclussen et al. [11].\nFigure 2\nFigure 2. Identification of the uterus.\nFigure 3\nFigure 3. Excision of a uterine horn segment.\nFigure 4. Suturing of the uterine tissue to the peritoneal wall.Figure 4\nwww.eCERM.org 3\nSitumorang H Standardized endometriosis model in Sprague–Dawley rats\nAA\nCC\nBB\nDD\n\ntraperitoneal ceftriaxone at a dose of 10 mg per rat on postoperative \ndays 0, 1, and 2.\n4. Lesion assessment\nOne month later, a second laparotomy was performed under the \nsame anesthesia and asepsis protocol. A 4-cm midline incision was \nmade, and the peritoneal cavity was inspected. Macroscopic features \nof endometriotic lesions were documented and photographed using \nan iPhone 7 Plus camera (Apple Inc.) with a millimeter scale for cali-\nbration (Figure 5).\n5. Histological analysis\nLesions were excised and immediately fixed in 10% buffered for-\nmalin. Tissues were processed through graded alcohols, cleared in \nxylene, and embedded in paraffin. Serial sections were cut using a \nmicrotome, mounted on glass slides, and stained with hematoxylin \nand eosin (H&E). Microscopic evaluation was performed using a \nstandard light microscope at 40× to 400× magnification.\n6. Postoperative care\nAnimals were monitored daily for signs of distress, wound healing, \nand general health status. No intraoperative or postoperative mor-\ntality occurred. At the conclusion of the study, all rats were eutha-\nnized by decapitation under deep anesthesia.\nResults\nAll 60 rats (100%) developed macroscopically visible endometriot-\nic lesions, indicating that each implanted endometrial fragment suc-\ncessfully formed a lesion using the modified Vivian technique. At the \nsecond laparotomy, performed 1 month after implantation, cystic le-\nsions were consistently identified on the peritoneal surface. Lesions \nappeared as fluid-filled, cystic masses with smooth surfaces and a \nhyperemic coloration compared with the surrounding peritoneal tis-\nsue. Prominent blood vessels converged toward the lesions, and ad-\nhesions to adjacent bowel or omentum were observed in several an-\nimals (Figure 6). The surface area of each lesion was documented by \ndigital photography with a millimeter scale and subsequently mea-\nsured using SketchAndCalc software (iCalc Inc.).\nQuantitative measurements demonstrated expected biological \nvariability, with lesion areas ranging from 0.83 to 131.50 mm² (mean, \n45.27 mm²; median, 37.34 mm²) across the cohort (Table 1). This dis-\ntribution aligns with prior reports of surgically induced endometrio-\nsis, in which lesion heterogeneity is typical despite standardized im-\nplantation techniques (Figure 7). The uniformly successful lesion for-\nmation observed in the present study compares favorably with earli-\ner models, which often report 60% to 80% viability because of incon-\nsistent graft orientation, limited suture fixation, or suboptimal es-\ntrous timing at implantation.\nHistological analysis of excised lesions further confirmed the es-\ntablishment of endometriotic tissue. H&E staining demonstrated \ncystic structures lined by a single layer of cuboidal epithelial cells, \nwith surrounding endometrial-like glands and stromal components. \nStromal cellularity was most pronounced adjacent to the cyst wall \nand gradually decreased toward the periphery, consistent with orga-\nnized tissue architecture within the implants (Figures 8 and 9).\nDiscussion\nThis study established a standardized rat model of endometriosis \nwith a 100% lesion induction rate, exceeding the success typically re-\nported in classical models such as Vernon and Wilson [9] and the \noriginal Vivian technique. The high reproducibility observed here \nlikely reflects several purposeful refinements. First, implantation was \nFigure 5.  Macroscopic appearance of the lesion and area measurement. (A) Representative macroscopic image of the lesion. (B) \nRepresentative macroscopic image after area measurement using SketchAndCalc software (iCalc Inc.).Figure 5A Figure 5B\nFigure 5A Figure 5B\nhttps://doi.org/10.5653/cerm.2025.086904\nClin Exp Reprod Med [Epub ahead of print]\nAA BB\n\nFigure 6. (A) Endometriotic lesion and (B) endometriotic lesion with intestinal adhesion.\nFigure 6A Figure 6B\nFigure 6A Figure 6B\nAA BB\nTable 1. Lesion area distribution after surgical induction of endo-\nmetriosis in rats\nParameter Value\nNumber\na)\n60\nMinimum area (mm\n2\n) 0.83\nMaximum area (mm\n2\n) 131.50\nMean area (mm\n2\n) 45.27\nMedian area (mm\n2\n) 37.34\nLesion areas were measured from standardized digital photographs con-\ntaining a millimeter reference marker and analyzed using SketchAndCalc \nplanimetry software.\na)\nThe number of rats with successfully established lesions at second laparot-\nomy (100% induction rate).\nFigure 7. Distribution of endometriotic lesion area in the rat model. Scatter plot showing the distribution of lesion area measurements.\nperformed exclusively during the proestrus or estrus phase, when \nendogenous estrogen levels peak, thereby providing a hormonally \nfavorable environment that supports endometrial cell survival, at-\ntachment, and subsequent growth [9,10,12]. Second, the uterine im-\nplant was fixed using four interrupted 6–0 nylon sutures, ensuring \nuniform apposition of the endometrial surface to the peritoneum \nand reducing the risk of graft detachment, a recognized limitation of \nearlier two-suture techniques. This more comprehensive anchoring \nlikely contributed substantially to consistent lesion establishment \nacross animals. Third, perioperative prophylactic antibiotic adminis-\ntration may have reduced postoperative infection, thereby limiting \ninflammatory complications that can compromise graft viability. Col-\nSize of endometriosis lesion (mm\n2\n)\n120\n100\n80\n60\n40\n20\n0 10 20 30 40 50 60\nNumber of rats\nwww.eCERM.org 5\nSitumorang H Standardized endometriosis model in Sprague–Dawley rats\n\nlectively, these modifications improved procedural stability, ad -\ndressed key limitations of prior rodent endometriosis models, and \nenabled reliable lesion formation.\nRodent models of endometriosis are broadly categorized as ho-\nmologous or heterologous. Homologous models, such as ours, use \nautologous or syngeneic uterine tissue transplanted into the perito-\nneal cavity, whereas heterologous models use human tissue in im-\nmunocompromised hosts [13]. Despite phylogenetic limitations, rat \nmodels remain widely used because they balance affordability, sur-\ngical feasibility, and preservation of immunological integrity. Our \nfindings support the use of standardized homologous models as re-\nliable preclinical platforms and complement menstrual-mimicry ap-\nproaches, such as those proposed by Persoons et al. [14].\nA defining feature of this model was the consistent development \nof neovascularization and adhesions, both of which are hallmarks of \nclinically significant endometriotic disease. Angiogenesis is essential \nfor the survival and expansion of ectopic endometrial implants and \nis largely mediated by vascular endothelial growth factor (VEGF), \nwhich has been repeatedly implicated as a central driver of lesion \nvascularization in rodent and human studies [15,16]. Although VEGF \nexpression was not quantified, the pronounced macroscopic neovas-\ncularization observed aligns with established angiogenic mecha-\nnisms and supports the biological validity of the induced lesions. \nSimilarly, the frequent formation of adhesions—often underreport-\ned in rodent models despite their contribution to infertility, dyspa-\nreunia, and chronic pelvic pain—enhances the translational rele -\nvance of this approach [13].\nThe inflammatory microenvironment also underpins these patho-\nlogical processes. Activated macrophages and pro-inflammatory cy-\ntokines, particularly tumor necrosis factor alpha (TNF-α), promote \nFigure 7A Figure 7b\nFigure 8. Histologic appearance of rat endometriotic lesions (hematoxylin and eosin stain). (A) Tissue section from the endometriosis model (40×). \nScale bar: 0.1 mm. (B) Cystic lesion containing endometrial cells and leukocytes; the cyst wall is lined by a single layer of cuboidal epithelium (yellow \narrow) (40×). Cystic lesion surrounded by endometrial-like stroma and gland-like structures (pink arrow) (40×). Scale bar: 0.1 mm.\nFigure 8A Figure 8b\nFigure 8A Figure 8b\nFigure 9. (A) High-power view of the cyst wall and surrounding endometrial-like tissue (hematoxylin and eosin stain). Cystic lesion \ncontaining endometrial cells and leukocytes; the cyst wall is lined by a single layer of cuboidal epithelium (yellow arrow) (400×). (B) Cystic \nlesion surrounded by endometrial-like stroma and gland-like structures (arrowhead) (400×). Scale bar: 0.1 mm.\nhttps://doi.org/10.5653/cerm.2025.086906\nClin Exp Reprod Med [Epub ahead of print]\nAA\nAA\nBB\nBB\n\nimplantation, persistence, and progression of ectopic endometrium, \nwhile emerging mediators such as interleukin 37 correlate with dis-\nease severity and may serve as biomarkers of lesion activity [17,18]. \nAlthough cytokine profiles were not measured in this study, the \nmacroscopic and histological findings—cystic morphology, promi-\nnent vascularization, and well-preserved glandular and stromal ar-\nchitecture—are consistent with inflammatory cascades described in \ncontemporary rodent endometriosis models. H&E staining provided \nmorphological confirmation; however, current evidence suggests \nthat optimal validation of experimentally induced lesions includes \nimmunohistochemical (IHC) markers to substantiate tissue identity, \ndistinguish endometriotic implants from nonspecific peritoneal reac-\ntions, and assess angiogenic or inflammatory activity [19]. The ab-\nsence of molecular and IHC analyses therefore represents a method-\nological limitation, particularly because current standards emphasize \nevaluation of mediators such as TNF-α, VEGF , and oxidative stress \nmarkers (e.g., malondialdehyde) to strengthen mechanistic interpre-\ntation and translational relevance. Future applications of this stan-\ndardized model should incorporate targeted molecular and IHC as-\nsays to enhance lesion characterization, support reproducibility, and \nimprove comparability with human disease.\nOxidative stress also plays a central role in endometriosis patho-\nphysiology. Reactive oxygen species and byproducts such as \nmalondialdehyde contribute to peritoneal inflammation and cellular \nstress, which may promote lesion persistence and impair reproduc-\ntive function [6]. The interaction between oxidative stress and in-\nflammation has been linked to infertility in both clinical and experi-\nmental studies, underscoring the value of incorporating oxidative \nstress biomarkers in future applications of this model.\nThese findings are also consistent with evidence showing repro-\nductive consequences of endometriosis in rats, including impaired \novarian reserve and reduced fertility [6]. By reliably inducing lesions \nwith adhesion formation, this model provides a robust framework \nfor investigating how endometriosis disrupts reproductive function \nand for evaluating targeted interventions. Pharmacological studies \nhave shown that agents such as rosiglitazone can reduce lesion pro-\ngression in surgically induced rat models, further illustrating the utili-\nty of standardized systems for preclinical drug testing [20].\nSeveral limitations should be acknowledged. First, rodents do not \nmenstruate, which limits the extent to which retrograde menstrua-\ntion can be modeled as a mechanism of disease establishment \n[7,14]. Second, pain assessment—an essential translational end -\npoint—was not included and should be prioritized in future studies \n[5]. Third, molecular and IHC evaluation of angiogenic, inflammatory, \nand oxidative stress pathways would complement the morphologi-\ncal findings reported here. In addition, the present method specifi-\ncally generates peritoneal wall endometriosis, whereas human dis-\nease encompasses multiple subtypes, including superficial peritone-\nal lesions, deep infiltrating endometriosis, and ovarian endometrio-\nmas. Developing parallel protocols to model these phenotypes, and \nclearly subclassifying experimental models accordingly, would im-\nprove translational applicability and better reflect clinical heteroge-\nneity [21].\nIn conclusion, this modified rat model of endometriosis reliably re-\ncapitulates essential disease features, including vascularization, cyst \nformation, and adhesion development. The reproducibility achieved \nin the present study supports its use as a platform for mechanistic \nstudies and preclinical evaluation of novel therapies. Future research \nshould extend this framework by incorporating molecular validation \nand pain phenotyping to better align experimental outcomes with \nthe clinical complexity of endometriosis.\nConflict of interest\nNo potential conflict of interest relevant to this article was reported.\nORCID\nHerbert Situmorang https://orcid.org/0000-0001-7370-5819\nReferences\n1. Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J \nMed 2020;382:1244-56.\n2. Taylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic sys-\ntemic disease: clinical challenges and novel innovations. Lancet \n2021;397:839-52.\n3. Chapron C, Marcellin L, Borghese B, Santulli P . Rethinking mecha-\nnisms, diagnosis and management of endometriosis. Nat Rev En-\ndocrinol 2019;15:666-82.\n4. Burns KA, Pearson AM, Slack JL, Por ED, Scribner AN, Eti NA, et al. \nEndometriosis in the mouse: challenges and progress toward a \n‘best fit’ murine model. Front Physiol 2021;12:806574.\n5. Tejada MA, Antunez C, Nunez-Badinez P , De Leo B, Saunders PT, \nVincent K, et al. Rodent animal models of endometriosis-associat-\ned pain: unmet needs and resources available for improving trans-\nlational research in endometriosis. Int J Mol Sci 2023;24:2422.\n6. Kanellopoulos D, Karagianni D, Pergialiotis V, Nikiteas N, Lazaris \nAC, Iliopoulos D. The effect of endometriosis on fertility in an ani-\nmal model. J Med Life 2022;15:1170-5.\n7. Ajayi AF , Akhigbe RE. Staging of the estrous cycle and induction \nof estrus in experimental rodents: an update. Fertil Res Pract \n2020;6:5.\n8. Jones RC. The effect of a luteinizing hormone releasing hormone \nwww.eCERM.org 7\nSitumorang H Standardized endometriosis model in Sprague–Dawley rats\n\n(LRH) agonist (Wy-40,972), levonorgestrel, danazol and ovariec-\ntomy on experimental endometriosis in the rat. Acta Endocrinol \n(Copenh) 1984;106:282-8.\n9. Vernon MW, Wilson EA. Studies on the surgical induction of endo-\nmetriosis in the rat. Fertil Steril 1985;44:684-94.\n10. do Amaral VF , Dal Lago EA, Kondo W, Souza LC, Francisco JC. De-\nvelopment of an experimental model of endometriosis in rats. \nRev Col Bras Cir 2009;36:250-5.\n11. Zenclussen ML, Casalis PA, Jensen F , Woidacki K, Zenclussen AC. \nHormonal fluctuations during the estrous cycle modulate heme \noxygenase-1 expression in the uterus. Front Endocrinol (Laus-\nanne) 2014;5:32.\n12. Pereira FE, Almeida PR, Dias BH, Vasconcelos PR, Guimaraes SB, \nMedeiros Fd. Development of a subcutaneous endometriosis rat \nmodel. Acta Cir Bras 2015;30:6-12.\n13. Abdolmaleki A, Jalili C, Mansouri K, Bakhtiari M. New rat to mouse \nxenograft transplantation of endometrium as a model of human \nendometriosis. Animal Model Exp Med 2021;4:268-77.\n14. Persoons E, De Clercq K, Van den Eynde C, Pinto SJ, Luyten K, Van \nBree R, et al. Mimicking Sampson’s retrograde menstrual theory \nin rats: a new rat model for ongoing endometriosis-associated \npain. Int J Mol Sci 2020;21:2326.\n15. Chung MS, Han SJ. Endometriosis-associated angiogenesis and \nanti-angiogenic therapy for endometriosis. Front Glob Womens \nHealth 2022;3:856316.\n16. Powell SG, Sharma P , Masterson S, Wyatt J, Arshad I, Ahmed S, et \nal. Vascularisation in deep endometriosis: a systematic review \nwith narrative outcomes. Cells 2023;12:1318.\n17. Cao XL, Chai J, Yu YY, Tian X, Zhao JY, Yu LY, et al. Association of \nTNF-α gene T-1031C polymorphism with endometriosis: a me-\nta-analysis. Am J Reprod Immunol 2020;84:e13305.\n18. Jiang J, Jiang Z, Xue M. Serum and peritoneal fluid levels of inter-\nleukin-6 and interleukin-37 as biomarkers for endometriosis. Gy-\nnecol Endocrinol 2019;35:571-5.\n19. Bratila E, Bratila CP , Comandasu DE, Bausic V, Vladescu CT, Mehed-\nintu C, et al. The assessment of immunohistochemical profile of \nendometriosis implants, a practical method to appreciate the ag-\ngressiveness and recurrence risk of endometriosis. Rom J Mor-\nphol Embryol 2015;56:1301-7.\n20. Zhang S, Zhuang L, Liu Q, Yu X, Min Q, Chen M, et al. Rosiglitazone \naffects the progression of surgically induced endometriosis in a \nrat model. Mol Med Rep 2021;23:35.\n21. Golabek-Grenda A, Olejnik A. In vitro modeling of endometriosis \nand endometriotic microenvironment: challenges and recent ad-\nvances. Cell Signal 2022;97:110375.\nhttps://doi.org/10.5653/cerm.2025.086908\nClin Exp Reprod Med [Epub ahead of print]","source_license":"public-domain-us","license_restricted":false}