{"paper_id":"d5ec5c65-8d15-437e-bff0-a0d53c4ab40a","body_text":"Journal of Biosciences and Medicines, 2025, 13(11), 209-225 \nhttps://www.scirp.org/journal/jbm \nISSN Online: 2327-509X \nISSN Print: 2327-5081 \n \nDOI: 10.4236/jbm.2025.1311015  Nov . 11, 2025 209 Journal of Biosciences and Medicines \n \n \n \n \nPathological Interaction Mechanisms between \nCervical Mycoplasma and Chlamydia  \nInfections and Endometriosis: Novel  \nClinical Management Strategies \nZhaodong Wei, Cunjian Yi* \nDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Yangtze University, Jingzhou, China \n \n \n \nAbstract \nEndometriosis (EMs), a prevalent chronic inflammatory disease among women \nof reproductive age, has a global prevalence of 10% - 15% and is closely asso-\nciated with 30% - 50% of infertility cases. This review systematically examines \nthe epidemiological characteristics and molecular pathogenesis of EMs, estab-\nlishing for the first time a dynamic interaction model between cervical myco-\nplasma and chlamydia infections in the pat hological progression of EMs. \nBased on epidemiological correlation analysis, it reveals the spatiotemporal \nassociation between genital tract infections and EMs onset. By examining in-\nflammatory pathway interactions, immune dysregulation, and microbiome \nimbalance, it elucidates the potential infection -inflammation-endometriosis \n“pathological vicious cycle”. Clinically, it innovatively proposes a “dual-track \ntreatment” strategy integrating targeted hormone therapy, precision anti -in-\nfective regimens, and combined immune -microbiome modulation. This re-\nview constructs a precision prevention and treatment system through a trans-\nlational medicine perspective. It not only achieves a paradigm shift in diagno-\nsis and treatment from “symptom control” to “etiological intervention” but \nalso provides EM patients with personalized treatment pathways based on mo-\nlecular subtyping. This breakthrough offers a novel methodological frame-\nwork for addressing treatment resistance and recurrence prevention in EM. \n \nKeywords \nEndometriosis (EMs), Immune Dysregulation, Chronic Inflammation,  \nMycoplasma and Chlamydia Infections \n \n \n*Corresponding author. \nHow to cite this paper: Wei, Z.D. and Yi, \nC.J. (2025) Pathological Interaction Mecha-\nnisms between Cervical Mycoplasma and \nChlamydia Infections and Endometriosis: \nNovel Clinical Management Strategies. \nJournal of Biosciences and Medicines, 13, \n209-225. \nhttps://doi.org/10.4236/jbm.2025.1311015 \n \nReceived: October 11, 2025 \nAccepted: November 8, 2025 \nPublished: November 11, 2025 \n \nCopyright © 2025 by author(s) and  \nScientific Research Publishing Inc. \nThis work is licensed under the Creative \nCommons Attribution International  \nLicense (CC BY 4.0). \nhttp://creativecommons.org/licenses/by/4.0/   \n  \nOpen Access\n\nZ. D. Wei, C. J. Yi \n \n \nDOI: 10.4236/jbm.2025.1311015 210 Journal of Biosciences and Medicines \n \n1. Introduction \nEndometriosis is a common chronic gynecological disorder among women of re-\nproductive age. Clinically, it manifests as the growth of endometrioid tissue out-\nside the uterine cavity, primarily distributed within the pelvic cavity — including \nthe ovaries, fallopian tubes, peritoneum, and bladder surface. Its global prevalence \nis approximately 10%, rising to 30% - 50% among women with infertility  [1]. \nSymptoms of endometriosis exhibit high heterogeneity, including chronic pelvic \npain, menstrual irregularities, infertility, and dyspareunia. These symptoms sig-\nnificantly impact patients ’ quality of life and mental health [2]. The etiology of \nendometriosis is complex, and its pathogenesis remains incompletely understood. \nCurrent mainstream theories include retrograde menstruation, immune dysregu-\nlation, genetic susceptibility, and stem cell mechanisms. Retrograde menstruation \nis considered the primary source of ectopic endometrial implantation, yet not all \nwomen develop endometriosis , suggesting other factors — such as immune dys-\nfunction and inflammatory responses— play crucial roles in disease onset and pro-\ngression [3]. Concurrently, Mycoplasma and Chlamydia infections of the cervix, \nas the most prevalent sexually transmitted infections in the female reproductive \ntract, impact reproductive health through their chronic and insidious nature. \nThese pathogens not only cause chronic pelvic inflammation but are also fre-\nquently associated with reproductive disorders, such as tubal obstruction, infer-\ntility, and recurrent miscarriage. In recent years, increasing research has focused \non the potential interplay between Mycoplasma and Chlamydia infections and \nendometriosis, particularly at the level of shared inflammatory a nd immunoreg-\nulatory mechanisms. \nWhile \nUreaplasma urealyticum and Chlamydia trachomatis infections are pre-\ndominantly associated with pelvic inflammatory disease and reproductive disor-\nders, their direct link to endometriosis remains incompletely understood. Some \nstudies suggest these pathogens may interact with endometriosis through shared \ninflammatory pathways. For instance, Ureaplasma infection significantly upregu-\nlates TNF-\nα and IL-1β expression— inflammatory mediators also demonstrated \nto be markedly elevated in endometriosis  [4]. Similarly, Chlamydia trachomatis \ninfection may influence the formation and progression of endometriosis by dis-\nrupting mucosal barriers, activating the innate immune system, and promoting \ninflammatory responses and tissue fibrosis [5]. This review will therefore examine \nthe epidemiological characteristics, potential associative mechanisms, and current \nclinical interventions regarding endometriosis and cervical Mycoplasma/Chla-\nmydia infections, while also outlining future research directions and clinical man-\nagement strategies. \n2. Endometriosis \n2.1. Pathogenesis of Endometriosis \nThe early classical theory, the Retrograde Menstruation Theory, posits that during \nmenstruation, fragments of endometrial tissue flow retrograde through the fallo-\n\nZ. D. Wei, C. J. Yi \n \n \nDOI: 10.4236/jbm.2025.1311015 211 Journal of Biosciences and Medicines \n \npian tubes into the pelvic cavity, implanting at ectopic sites to form lesions. This \ntheory provides a crucial foundation for explaining the origin of ectopic endome-\ntrial tissue. However, retrograde menstruation is also common in healthy women, \nsuggesting that retrograde flow alone is insufficient to induce endometriosis. Con-\nsequently, researchers further explored that abnormalities in host immune func-\ntion may be crucial for the implantation and survival of ectopic endometrial tis-\nsue. In patients with endometriosis, natural killer (NK) cell activity is significantly \nreduced, and macrophage clearance function is weakened. This impairs the timely \nremoval of endometrial tissue entering the pelvic cavity, allowing it to survive and \nform ectopic lesions. Furthermore, ectopic endometrial tissue itself secretes large \namounts of pro-inflammatory cytokines (such as IL-1\nβ, TNF-α, IL-6, etc.). These \nfactors further activate local pelvic inflammatory responses and immune system \ndysregulation, creating an “inflammation -immune abnormality” environment \nthat ultimately promotes disease progression. \nEndometriosis exhibits distinct hormone -dependent characteristics. Research \nindicates that the root cause of significantly elevated estrogen levels within ectopic \nlesions lies in the abnormally high expression of aromatase (CYP19A1). As the \nkey enzyme conv erting androgens to estrogens, aromatase becomes hyperactive \nat lesion sites, continuously converting androgens into estrogens. This creates a \nlocalized “high estrogen environment,” stimulating persistent growth and prolif-\neration of ectopic endometrial tis sue, thereby driving disease progression. Con-\ncurrently, ectopic endometrial tissue exhibits resistance to progesterone, known \nas progesterone resistance. Under normal circumstances, progesterone effectively \nsuppresses endometrial cell proliferation and maintains endometrial homeostasis. \nHowever, in this disease, endometrial tissue responds poorly to progesterone, di-\nminishing its antiproliferative capacity and preventing effective control of ectopic \nendometrial proliferation. The negative effects of estrogen  extend beyond pro-\nmoting endometrial growth. It also activates inflammatory pathways such as the \nNF-\nκB pathway, further stimulating local inflammatory responses. This exacer-\nbates tissue damage and immune imbalance, driving disease progression. \nGenetic studies indicate familial clustering in endometriosis. Genome-wide as-\nsociation studies (GWAS) have identified multiple disease-associated genetic loci, \nincluding WNT4, VEZT, GREB1, and FN1. These genes play crucial roles in reg-\nulating endometrial t issue adhesion, migration, and invasiveness. For instance, \nVEZT gene overexpression enhances ectopic tissue adhesion to surrounding stroma, \nwhile GREB1 abnormalities likely accelerate disease progression by disrupting es-\ntrogen signaling pathways. Endometriotic lesions exhibit tumor-like characteris-\ntics, primarily manifested as abnormal, increased angiogenesis, and enhanced in-\nvasiveness. High expression of matrix metalloproteinases (MMP -2 and MMP-9) \nwithin lesions promotes degradation of the basement membrane and extracellular \nmatrix, enhancing the migration and invasiveness of ectopic tissue. Concurrently, \nelevated vascular endothelial growth factor (VEGF) levels in ectopic tissues stim-\nulate neovascularization, supplying essential blood flow and nutrients to  sustain \n\nZ. D. Wei, C. J. Yi \n \n \nDOI: 10.4236/jbm.2025.1311015 212 Journal of Biosciences and Medicines \n \nlesion survival. This perpetuates ectopic foci, complicating therapeutic manage-\nment. \n \n \n2.2. Local Effects of Chronic Inflammation \nA prominent pathological feature of endometriosis lies in the ability of ectopic \nlesions to secrete multiple inflammatory mediators, thereby establishing a persis-\ntent chronic inflammatory state within the pelvis. Research indicates that ectopic \nendometrial tissue secretes pro-inflammatory factors such as IL-1, IL-6, and TNF-\nα. These mediators not only activate macrophages and neutrophils in the pelvis, \ncreating a stable pro -inflammatory environment, but also disrupt normal tissue \nstructures, leading to issues like tubal obstruction and local fibrosis  [6]-[8]. Pro-\nlonged inflammatory stimulation promotes excessive collagen deposition, trigger-\ning fibrosis in the lesions and surrounding tissues. This not only impairs repro-\nductive organ function but also makes complete surgical removal of the lesions \ndifficult [6]. Furthermore, nerve growth factor (NGF) secreted by ectopic lesions \ncan induce local neurosensitization and abnormal neurogenic connections, fur-\nther exacerbating the patient’s chronic pain state. \nMore notably, persistent chronic pelvic inflammation may compromise the lo-\ncal mucosal barrier and induce immune dysregulation, thereby increasing cervical \nsusceptibility to pathogens. Research indicates that under chronic inflammatory \nconditions, excessive release of pro-inflammatory mediators and immune imbal-\nance create favorable conditions for Mycoplasma and Chlamydia adhesion and \ninvasion, forming an “infection-inflammation-ectopic” cycle that may exacerbate \nendometriosis progression [9] [10]. \n2.3. Microbiome Dysbiosis and Endometriosis \nIn recent years, the potential impact of the reproductive tract microbiome on en-\ndometriosis has garnered increasing attention. Studies reveal significantly reduced \n\n\nZ. D. Wei, C. J. Yi \n \n \nDOI: 10.4236/jbm.2025.1311015 213 Journal of Biosciences and Medicines \n \nmicrobial diversity in the reproductive tract of endometriosis patients, character-\nized by decreased dominant bacteria (e.g., lactobacilli) and increased proportions \nof opportunistic pathogens (e.g., Ureaplasma urealyticum and Chlamydia tracho-\nmatis) [11]. These microbial alterations may influence disease through multiple \nmechanisms: Ureaplasma and Chlamydia infections can induce massive pro -in-\nflammatory factor secretion, activating inflammatory mediators that directly or \nindirectly exacerbate endometriotic lesions [12]. Additionally, dysbiosis may com-\npromise mucosal barrier function, impairing the immune system’s ability to clear \nectopic endometrial tissue. \n3. Characteristics of Mycoplasma and Chlamydia Infections \n3.1. Characteristics of Cervical Mycoplasma and Chlamydia  \nInfections and Their Relationship with Reproductive  \nSystem Diseases \nCervical Mycoplasma and Chlamydia infections are the most common sexually \ntransmitted infections (STIs) in the female reproductive system, with Ureaplasma \nurealyticum and Chlamydia trachomatis being the primary pathogens. \nUreaplasma urealyticum is a small pathogen lacking a cell wall. Under specific \nconditions, such as immunosuppression or microecological imbalance, it can trans-\nform into a pathogenic bacterium. Characteristics of Ureaplasma urealyticum in-\nfection include high infection rates and stealthiness. Studies indicate that Ureaplasma \nurealyticum carriage rates among sexually active women reach 40% - 80%, though \nmost infected individuals exhibit no apparent symptoms [11] [12]. Prolonged \nchronic infection may lead to pelvic inflammatory disease, salpingitis, infertility, \nand pregnancy complications [13]. Notably, Ureaplasma urealyticum induces lo-\ncal immune dysregulation and tissue damage by adhering to epithelial cells and \nsecreting toxic factors and inflammatory mediators. This chronic inflammatory \nenvironment within the pelvis may interact with the development and progression \nof endometriosis: on one hand, persistent inflammation and immune abnormali-\nties provide a “fertile ground” for ectopic endometrial tissue to adhere, grow, and \nundergo angiogenesis; On the other hand, the preexisting inflammatory back-\nground or dysbiosis in endometriosis patients may further increase susceptibility \nto Ureaplasma infection, thereby forming an “infection -inflammation-endome-\ntriosis” cycle. \nChlamydia trachomatis is another common genital tract pathogen. Chlamydia \ninfections are typically asymptomatic, potentially leading to missed treatment \nwindows and progression to chronic pelvic inflammatory disease, tubal obstruc-\ntion, infertility, and ectopic pregnancy [14]. Chlamydia trachomatis survives and \nreplicates within host cells through conversion between the reticulate and primary \nforms, evading immune recognition while releasing inflammatory mediators that \ndisrupt the genital tract mucosal barrier [15]. Research indicates that Chlamydia \ntrachomatis infection may trigger systemic immune responses, further impairing \nreproductive function [16]. Therefore, in-depth investigation of the bidirectional \n\nZ. D. Wei, C. J. Yi \n \n \nDOI: 10.4236/jbm.2025.1311015 214 Journal of Biosciences and Medicines \n \neffects of these pathogens on the reproductive tract microenvironment, immune \nmechanisms, and endometriotic lesions holds significant importance for main-\ntaining female reproductive health. \n3.2. How Anatomical and Physiological Characteristics  \nMake the Cervix a Primary Site for Mycoplasma  \nand Chlamydia Infections \nThe cervix is a high- risk site for infections in the female reproductive tract, with \nits unique anatomical and physiological characteristics determining its high sus-\nceptibility to pathogens. Located at the junction of the lower and upper reproduc-\ntive tracts, the cervix possesses a complex anatomical structure and mucosal bar-\nrier function, playing a vital role in maintaining reproductive tract health and pre-\nventing pathogen invasion. However, under certain specific conditions, these bar-\nrier functions may be compromised, thereby increasing the risk of infection. \nThe mucus secreted by cervical glands forms a vital barrier against ascending \ninfections. Its viscosity and composition undergo dynamic changes throughout \nthe menstrual cycle under hormonal influence [17]. During ovulation, the mucus \nthins to facilitate sperm passage; by the luteal phase, it thickens to enhance de-\nfense. However, pathogens like \nUreaplasma urealyticum can compromise barrier \nfunction by secreting enzymes that degrade mucus components or reducing anti-\nmicrobial peptides (e.g., defensins, lysozyme) within it [18]. \nThe squamo-columnar junction of the cervix represents a transitional zone be-\ntween squamous and columnar epithelium. Here, newly generated cells exhibit high \nactivity but an immature barrier, with loose intercellular connections that facilitate \npathogen adhesion and invasion [19]. Chlamydia trachomatis and Ureaplasma urea-\nlyticum bind to epithelial cells via surface adhesion proteins, achieving coloniza-\ntion and replication in this region  [20]. Chronic inflammation further damages \nlocal epithelium, increasing genetic mutation risk and elevating susceptibility to \nother cervical pathologies. These dual characteristics render the cervix highly sus-\nceptible to pathogens like mycoplasma and chlamydia. Any factor weakening the \nmucus barrier or altering local epithelial structure— such as hormonal imbalances \nor microbiome disruption— may heighten infection risk and foster persistent in-\nflammation within the pelvic cavity. \nThe cervical microenvironment provides multiple conditions conducive to \npathogen growth and reproduction. Under normal circumstances, the cervical \nmicroecology maintains an optimal acidic pH (approximately 4.0) through the \nmetabolic activity of lactobacilli, thereby inhibiting the growth of most pathogens \n[21]. However, when microecological imbalance occurs (e.g., reduced lactobacilli \nor increased proportion of opportunistic pathogens), local pH may rise, compro-\nmising the natural anti-infective barrier. For instance, excessive antibiotic use or \npoor hygiene practices may disrupt the vaginal microbiota, creating favorable con-\nditions for \nChlamydia trachomatis and Ureaplasma urealyticum proliferation. Ad-\nditionally, the humidity and temperature conditions within cervical tissue support \nthe survival and transmission of these pathogens [22]. \n\nZ. D. Wei, C. J. Yi \n \n \nDOI: 10.4236/jbm.2025.1311015 215 Journal of Biosciences and Medicines \n \nBeyond anatomical and microenvironmental factors, the cervical mucosa’s lo-\ncal immune characteristics also contribute to its susceptibility. Although the cer-\nvical mucosa harbors diverse immune cells (e.g., macrophages and T cells) and \nantibodies (e.g., IgA) capable of defending against pathogens, certain pathogens \npossess immune evasion mechanisms. For instance, Chlamydia trachomatis sup-\npresses host autophagy to evade immune clearance [23]. Ureaplasma urealyticum \ncan weaken the host immune response by mutating surface antigens, thereby es-\ntablishing persistent infection. \nThe anatomical and physiological characteristics of the cervix determine its role \nas a primary site for Mycoplasma and Chlamydia infections. These include its \nclean structure and the dynamics of its microenvironment [24]. Pathogens achieve \ninvasion and replication by disrupting the mucus barrier, adhering to susceptible \nareas, altering the local environment, or evading the immune system. These char-\nacteristics not only form a crucial basis for infection but also suggest that strength-\nening barrier protection and regulating the microenvironment in the cervical re-\ngion are vital for preventing related infections. \n3.3. Pathogenesis of Mycoplasma and Chlamydia Infections \nMycoplasma and Chlamydia infections represent the most prevalent pathogenic \ninfections in the female reproductive system, with complex pathogenesis involv-\ning multiple pathways and pathological changes. These pathogens colonize hosts \nthrough mechanisms including adhesion, invasion, and immune evasion, trigger-\ning local and systemic inflammatory responses. They may induce chronic patho-\nlogical damage, ultimately impairing reproductive function.[25]. \nUreaplasma urealyticum, a cell wall-deficient microorganism, relies on surface \nadhesion proteins to bind to host cells, enabling attachment and colonization on \nthe surface of cervical epithelial cells. Its unique adhesion mechanism allows it to \nfirmly attach to susceptible sites such as the squamocolumnar junction of the cer-\nvix, laying the groundwork for subsequent infection [24]. Furthermore, Ureaplasma \nreleases toxic substances during metabolism, such as urease and peroxides. These \nproducts not only directly damage host cell membranes but also exacerbate local in-\nflammatory responses by inducing oxidative stress [26]. Simultaneously, Ureaplasma \nactivates the host immune system, significantly upregulating the expression of \npro-inflammatory factors like IL -6 and TNF -\nα, attracting large numbers of im-\nmune cells to the infection site. This excessive immune response, while eliminat-\ning pathogens, also causes irreversible tissue damage. Particularly, its immune \nevasion capabilities— such as antigenic variation and suppression of complement \nactivation— enable it to evade immune surveillance long -term, leading to persis-\ntent infection and chronic inflammation. \nChlamydia trachomatis achieves infection and proliferation through its unique \nlife cycle [27]. Its elementary body (EB) adheres to host cell surfaces and enters \ncells via phagocytosis, transforming into a reticular body (RB) intracellularly. It \nrapidly replicates and forms inclusion bodies. This process not only disrupts host \n\nZ. D. Wei, C. J. Yi \n \n \nDOI: 10.4236/jbm.2025.1311015 216 Journal of Biosciences and Medicines \n \ncell structures but also expands infection by releasing inflammatory mediators. \nThe NF-κB signaling pathway activated during Chlamydia trachomatis infection \nsignificantly increases the secretion of pro-inflammatory cytokines such as IL-1β, \nIL-8, and IFN-γ. These factors sustain local inflammation through a self-amplify-\ning mechanism [28]. Furthermore, Chlamydia trachomatis exhibits potent immune \nevasion capabilities, such as suppressing host antigen presentation by downregulat-\ning MHC-I and MHC-II molecule expression, or evading clearance by interfering \nwith host autophagy pathways. These mechanisms collectively contribute to the \npersistence and refractory nature of its infection [29]. \n3.4. The Relationship Between Mycoplasma and Chlamydia  \nInfections and Chronic Inflammation \nWhether caused by Mycoplasma or Chlamydia infections, the common patho-\nlogical feature is tissue damage and functional abnormalities triggered by chronic \ninflammation [30]. This chronic inflammatory response extends beyond the lo-\ncal infection site, potentially spreading to surrounding tissues and even trigger-\ning systemic reactions. At the infection site, the release of numerous pro-inflam-\nmatory factors attracts macrophages and neutrophils. While these cells elimi-\nnate pathogens, they also release reactive oxygen species (ROS) and reactive ni-\ntrogen species (RNS), causing severe damage to host cells [31]. Such fibrosis is \na major cause of anatomical abnormalities like tubal obstruction and cervical \nstenosis, while also significantly increasing the risk of infertility and ectopic \npregnancy. \nChronic inflammation further exacerbates the pathological process by promot-\ning angiogenesis and altering the microenvironment. Under persistent inflamma-\ntory conditions, vascular endothelial growth factor (VEGF) levels rise significantly, \nleading to abnormal blood vessel formation. These neovessels not only supply nu-\ntrients and oxygen for pathogen survival and spread but may also worsen local \nhemorrhage and tissue destruction due to increased vascular fragility. Notably, \nChlamydia trachomatis infection may also trigger systemic immune dysregulation \nduring chronic inflammation, such as elevated systemic IL -1β and IFN-γ levels, \nthereby affecting other organ functions and potentially correlating with certain \nautoimmune diseases. \n4. Association between Endometriosis and Cervical  \nUreaplasma and Chlamydia Infections \nEndometriosis and cervical ureaplasma and chlamydia infections are two com-\nmon diseases of the female reproductive system. Although they differ in etiology \nand presentation, recent studies suggest a potential correlation between the two. \nChronic inflammation and immune dysregulation triggered by cervical infections \nmay promote the development of endometriosis, while the chronic inflammatory \nbackground in endometriosis patients may also increase susceptibility to patho-\ngen infections. \n\nZ. D. Wei, C. J. Yi \n \n \nDOI: 10.4236/jbm.2025.1311015 217 Journal of Biosciences and Medicines \n \n4.1. Epidemiological Evidence Supporting Correlation \nEpidemiological studies indicate significantly elevated rates of Mycoplasma and \nChlamydia infections among endometriosis patients, providing preliminary evi-\ndence for a potential association. A study of infertile women found Chlamydia \ninfection rates exceeding 30% in those with endometriosis, markedly higher than \nin women without the condition [32]. The prevalence of Ureaplasma infection is \nalso markedly elevated in endometriosis patients, particularly in the context of \nchronic pelvic inflammatory disease  [33]. This suggests that mycoplasma and \nchlamydia infections may promote the onset and progression of endometriosis \nthrough mechanisms such as inducing inflammation or immune dysregulation. \nHigher detection rates of mycoplasma and chlamydia infections are observed \nin patients with severe endometriosis. This reflects the role of pathogen infection \nin sustaining a chronic inflammatory environment and suggests a potentially mu-\ntually reinforcing vicious cycle between the two. While existing epidemiological \ndata provide important clues, limitations in sample size and inconsistent stand-\nards across studies restrict the generalizability of these findings [34]. \n4.2. Interactions among Inflammatory Pathways \nThe inflammatory response induced by Mycoplasma and Chlamydia infections is \nconsidered a key mechanism linking these pathogens to endometriosis [35]. My-\ncoplasma and Chlamydia infections are typically accompanied by local and sys-\ntemic inflammatory responses, manifested as elevated pro -inflammatory cyto-\nkines (e.g., IL-6, IL-1β, and TNF-α). These inflammatory mediators are also core \npathological factors in endometriosis, supporting the implantation and growth of \nendometrial cells migrating retrograde into the pelvis by enhancing local angio-\ngenesis and matrix degradation. \nStudies indicate that Chlamydia infection significantly amplifies local and sys-\ntemic inflammatory responses by activating the NF -κB signaling pathway. This \nmechanism closely parallels the abnormal inflammatory pathways observed in en-\ndometriosis patients. This shared inflammatory mechanism may represent a key \nlink in the correlation between the two conditions. Additionally, Ureaplasma  in-\nfection further exacerbates endometriosis by inducing excessive prostaglandin E2 \n(PGE2) secretion, thereby promoting vascul arization and dissemination of ec-\ntopic endometrial tissue [36] [37]. \nChronic inflammation not only supports the implantation and growth of ec-\ntopic endometrial tissue but also impairs the immune system ’s ability to clear it. \nImmune cells activated by the local inflammatory response— such as macrophages \nand neutrophils— release large amounts of reactive oxygen species and enzymatic \nsubstances while phagocytosing pathogens, causing damage to surrounding tis-\nsues. This chronic inflammatory environment may provide a crucial foundation \nfor the interaction between the two diseases. \n4.3. Impact of Immunomodulation \nBoth endometriosis and cervical Mycoplasma/Chlamydia infections are closely \n\nZ. D. Wei, C. J. Yi \n \n \nDOI: 10.4236/jbm.2025.1311015 218 Journal of Biosciences and Medicines \n \nassociated with immune dysregulation. Studies indicate that the immune systems \nof endometriosis patients exhibit significant immune evasion phenomena, such as \nreduced natural killer (NK) cell activity and impaired macrophage function. This \nimmune dysfunction facilitates the implantation and survival of endometrial tis-\nsue ascending into the pelvic cavity [35]. \nMycoplasma and Chlamydia infections further weaken host immune defenses \nthrough their immune evasion mechanisms (e.g., antigenic variation, suppression \nof host MHC molecule expression), establishing a chronic infection state. Further-\nmore, infection-induced disruption of the mucosal barrier and abnormal immune \nregulation may provide pathways for ectopic endometrial migration. For example, \nChlamydia infection significantly activates matrix metalloproteinases (e.g., MMP-\n2, MMP-9), promoting extracellular matri x degradation and thereby enhancing \nthe invasiveness of ectopic endometrial tissue. The interaction of these mecha-\nnisms may play a key role in the mutual promotion of both diseases. \n4.4. Role of Microbiome and Pelvic Environment \nEpidemiological evidence first suggests a “infection-first, ectopic-later” temporal \nassociation between lower genital tract pathogen infections and endometriosis \n(EMs): A cohort study in Taiwan Region covering 79,518 cases of cervical/vagini-\ntis patients showed that lower genital tract infections approximately doubled the \nrisk of subsequent EMs (adjusted HR = 2.01, 95% CI 1.91 - 2.12). This finding \nestablishes a population-based foundation for the “pathogen-microbiome-endo-\nmetriosis” triadic linkage [38]. \nAt the microbial level, a 2024 systematic review and meta-analysis published in \nPLOS One (8 population studies, n = 1063) indicated that compared to a normal \nmicrobiome dominated by lactobacilli, vaginal dysbiosis (BV/moderate BV) was \npositively correlated with EMs (pooled OR = 1.17), while Lactobacillus-dominant \nmicrobiomes may confer protective effects [39]. Metagenomic sequencing further \nrevealed dysbiosis patterns. Studies have shown that EMs patients exhibit signifi-\ncant loss of Lactobacillus iners in the vagina, accompanied by enrichment of op-\nportunistic pathogens such as Anaerococcus, Prevotella, Porphyro monas, and \nUreaplasma urealyticum, along with increased overall α-diversity. This suggests \nthat after disruption of the lactobacilli-mediated low pH barrier, anaerobic bacte-\nria and mycoplasmas gain a survival advantage  [40]. This microbial “displace-\nment” not only elevates local pH and weakens the mucosal barrier but also ampli-\nfies pro-inflammatory factors like IL -6 and TNF -\nα through the Toll -like recep-\ntor/NF-κB pathway, providing an inflammatory backdrop for ectopic endometrial \ncell adhesion, angiogenesis, and matrix remodeling. The causality of pathogen -\nmicrobiome interactions in lesion progression was further validated in animal \nstudies: In a mouse endometrioma (EMs) model, vaginal broad-spectrum antibi-\notic pretreatment or vaginal microbiota transplantation (VMT) from healthy do-\nnors significantly reduced lesion volume, decreased Ki -67 expression, and low-\nered IL-1\nβ/IL-6/TNF-α levels in peritoneal fluid. This effect was closely associated \n\nZ. D. Wei, C. J. Yi \n \n \nDOI: 10.4236/jbm.2025.1311015 219 Journal of Biosciences and Medicines \n \nwith NF-κB signaling inhibition. These findings suggest that restoring a Lactoba-\ncillus-dominant acidic ecosystem or inhibiting NF -κB-mediated inflammatory \npathways may represent promising microbiome- based therapeutic strategies for \nmanaging EMs. \nIn summary, vaginal Lactobacillus depletion and pH elevation induced by path-\nogens such as Mycoplasma and Chlamydia not only compromise the mucosal bar-\nrier but also trigger chronic inflammation and angiogenesis signals, creating a \n“soft landing” environment conducive to endometrial implantation and expan-\nsion. Future research may explore novel approaches for preventing and treating \nEMs through targeted probiotics, vaginal microbiome therapy (VMT), and com-\nbined microbiome-immunomodulatory interventions targeting NF-\nκB. \n4.5. Increased Susceptibility to Cervical Mycoplasma and  \nChlamydia in Endometriosis Patients \nThe chronic inflammation and immune dysregulation in endometriosis patients \nmay conversely increase their susceptibility to pathogen infections. On one hand, \nthe pro-inflammatory environment of ectopic lesions further activates local in-\nflammatory pathways, exacerbating damage to the cervical epithelial barrier  [7] \n[41]; On the other hand, chronic inflammation may compromise local immune \nbarriers, rendering the cervix more susceptible to Mycoplasma and Chlamydia \ninfections [42] [43]. This susceptibility not only increases the risk of infection oc-\ncurrence but may also lead to more severe infection manifestations and treatment \nchallenges. \nFurthermore, studies reveal significantly reduced diversity of the reproductive \ntract microbiota and increased proportions of opportunistic pathogens in endo-\nmetriosis patients, suggesting that susceptibility to infection may be influenced by \nmicrobiome imbalance. For instance, reduced lactobacilli may weaken local anti-\nmicrobial activity, while proliferation of opportunistic pathogens may intensify \ninflammatory responses [44]. This complex interplay between the microbiota and \nthe inflammatory environment offers a new interpretive dimension for the asso-\nciation between endometriosis and cervical infection. \n5. Discussions \nThis review analyzes the potential association between endometriosis and cervical \nMycoplasma/Chlamydia infections, examining their mutual influences on inflam-\nmation, immunity, and the microbiome, and subsequently explores targeted pre-\nvention and treatment strategies. Existing research suggests that chronic inflam-\nmation and immune dysregulation induced by cervical infections may promote \nthe onset and progression of endometriosis [45]-[47]. Conversely, the local or sys-\ntemic inflammatory state in endometriosis patients may increase susceptibility to \npathogens. However, studies on the specific mechanisms underlying this relation-\nship require further investigation. \nStudies confirm that high levels of pro -inflammatory cytokines (e.g., TNF -α, \n\nZ. D. Wei, C. J. Yi \n \n \nDOI: 10.4236/jbm.2025.1311015 220 Journal of Biosciences and Medicines \n \nIL-6, IL-1β) induced by Mycoplasma and Chlamydia infections also show a sig-\nnificant upward trend in endometriosis patients, suggesting mutual promotion \nthrough shared inflammatory pathways  [48] [49]. Infection-induced disruption \nof the mucosal barrier and dysbiosis may also provide a “fertile ground” for the \nimplantation of ectopic endometrial cells within the pelvis, further intensifying \nthe pathological process of endometriosis. While numerous \nin vitro and animal \nmodel studies have partially validated that infection exacerbates chronic pelvic \ninflammation, large-scale population cohort data remain lacking to clarify the true \nextent of infection’s impact on endometriosis pathogenesis. \nOur research reveals that endometriosis remains highly challenging to manage \nclinically. Current interventions often focus on controlling symptoms and pro-\ngression of individual conditions— such as hormone regulation and surgical ap-\nproaches for endometriosis, or antibiotic treatment for mycoplasma and chla-\nmydia infections. However, if significant interaction between these two factors \nexists, treatment strategies must urgently consider their potential mutual influ-\nence. Existing literature indicates that concurrently controlling inflammation and \ncorrecting microecological imbalances in infected patients may help reduce chronic \npelvic inflammation levels, thereby indirectly decreasing ectopic lesion implanta-\ntion and spread [50]. Combining anti-infective therapy with interventions such as \nimmunomodulation or probiotic supplementation may break the “infection -in-\nflammation-ectopic” cycle, enhancing clinical efficacy and reducing recurrence  \n[51]. However, due to the lack of unified screening criteria and large- scale pro-\nspective studies, the specific indications and efficacy evaluation of combined ther-\napy remain to be further established. \nThe rapid advancement of precision medicine offers new approaches to address \nthese challenges. Through multi-omics technologies such as genomics, transcriptom-\nics, and microbiomics, we can analyze individual differences between endometri-\nosis and cervical infections at the molecular level, identify high- risk populations, \nand implement personalized interventions targeting their immune, inflammatory, \nor microbiome characteristics. For instance, patients with specific inflammatory \ngene variants or dysbiotic micr obiomes may benefit more from targeted inflam-\nmatory inhibitor therapies or microbiome restoration strategies. Furthermore, de-\nveloping long -acting anti -inflammatory drugs and novel immunomodulators \ncould significantly enhance treatment efficacy for recurrent or refractory cases. \nAlthough existing studies preliminarily reveal potential links between endome-\ntriosis and cervical Mycoplasma or Chlamydia infections, larger -scale epidemio-\nlogical investigations and high -quality randomized controlled trials are still \nneeded to clarify the causal relationship between the two and the benefits of in-\ntervention. The application of multimodal studies (e.g., integrating imaging, mo-\nlecular diagnostics, and immunological assessments) can further elucidate the in-\ntersection of these two diseases at the inflammation -immunity-microenviron-\nment level, providing robust support for early screening and comprehensive pre-\nvention strategies. In the future, establishing a unified combined screening pro-\n\nZ. D. Wei, C. J. Yi \n \n \nDOI: 10.4236/jbm.2025.1311015 221 Journal of Biosciences and Medicines \n \ncess in clinical practice and exploring a comprehensive management model cen-\ntered on “anti-infection-inflammation control-microecological restoration” may \nsignificantly improve patient symptoms and long-term reproductive outcomes. \nIn summary, endometriosis and cervical Mycoplasma/Chlamydia infections \nmay interact through shared mechanisms involving inflammatory pathways, im-\nmune dysregulation, and microecological imbalance. Clarifying their specific as-\nsociations and implementing comb ined interventions not only deepens our un-\nderstanding of endometriosis pathogenesis but also holds promise for delivering \nmore precise and efficient diagnostic and therapeutic pathways for patients. With \nthe integration of more clinical evidence and multid isciplinary technologies, a \nmore comprehensive diagnostic and treatment system may emerge in the field of \nfemale reproductive health, offering new opportunities and directions for the pre-\nvention and management of such diseases. \nThe rapid advancement of precision medicine offers hope for the integrated \nmanagement of endometriosis and cervical infections. Genomics and multi-omics \ntechnologies enable deeper exploration of disease heterogeneity across patients, \nfacilitating the identification of high-risk populations and the delivery of person-\nalized prevention and treatment strategies. For instance, patients with specific in-\nflammatory gene mutations or dysbiotic microbiomes may benefit more from tar-\ngeted inflammatory inhibitor or micr obiota restoration strategies than conven-\ntional therapies [9] [52] [53]. Furthermore, developing long -acting anti-inflam-\nmatory drugs and immunomodulators for recurrent or refractory cases could sig-\nnificantly enhance treatment efficacy. \nConflicts of Interest \nThe authors declare no conflicts of interest regarding the publication of this paper. \nReferences \n[1] Giudice, L.C. and Kao, L.C. (2004) Endometriosis. The Lancet, 364, 1789-1799.  \nhttps://doi.org/10.1016/s0140-6736(04)17403-5 \n[2] Guo, S.-W. (2009) Epigenetics of Endometriosis. Molecular Human Reproduction , \n15, 587-607. https://doi.org/10.1093/molehr/gap064 \n[3] Burney, R.O. and Giudice, L.C. (2012) Pathogenesis and Pathophysiology of Endo-\nmetriosis. Fertility and Sterility, 98, 511-519.  \nhttps://doi.org/10.1016/j.fertnstert.2012.06.029 \n[4] Somer, A., Salman, N., Yalçın, I. and Ağaçfidan, A. (2006) Role of Mycoplasma Pneu-\nmoniae and Chlamydia Pneumoniae in Children with Community -Acquired Pneu-\nmonia in Istanbul, Turkey. \nJournal of Tropical Pediatrics, 52, 173-178.  \nhttps://doi.org/10.1093/tropej/fml017 \n[5] Wang, Z., Guo, S., Xie, Y., Tong, Y., Qi, W. and Wang, Z. (2024) Endometrial Ex-\npression of ERRβ and ERRγ: Prognostic Significance and Clinical Correlations in Se-\nvere Endometriosis. Frontiers in Endocrinology, 15, Article ID: 1489097.  \nhttps://doi.org/10.3389/fendo.2024.1489097 \n[6] De Andrade, V.T., Nácul, A.P., Dos Santos, B.R., Lecke, S.B., Spritzer, P.M. and \n\nZ. D. Wei, C. J. Yi \n \n \nDOI: 10.4236/jbm.2025.1311015 222 Journal of Biosciences and Medicines \n \nMorsch, D.M. (2017) Circulating and Peritoneal Fluid Interleukin-6 Levels and Gene \nExpression in Pelvic Endometriosis. Experimental and Therapeutic Medicine , 14, \n2317-2322. https://doi.org/10.3892/etm.2017.4794 \n[7] Wang, X.M., Ma, Z.Y. and Song, N. (2018) Inflammatory Cytokines IL-6, IL-10, IL-\n13, TNF-Alpha and Peritoneal Fluid Flora Were Associated with Infertility in Patients \nwith Endometriosis. European Review for Medical and Pharmacological Sciences, 22, \n2513-2518. \n[8] Yan, J., Liu, C., Zhao, H., Wang, C., Yao, H., Lu, Q., et al. (2020) A Cross-Sectional \nStudy on the Correlation between Cytokines in a Pelvic Environment and Tubal Fac-\ntor Infertility. BMC Pregnancy and Childbirth, 20, Article No. 644.  \nhttps://doi.org/10.1186/s12884-020-03322-y \n[9] Campos, G.B., Marques, L.M., Rezende, I.S., Barbosa, M.S., Abrão, M.S. and \nTimenetsky, J. (2018) Mycoplasma Genitalium Can Modulate the Local Immune Re-\nsponse in Patients with Endometriosis. Fertility and Sterility, 109, 549-560.e4.  \nhttps://doi.org/10.1016/j.fertnstert.2017.11.009 \n[10] Hillis, S.D., Owens, L.M., Marchbanks, P.A., Amsterdam, L.E. and Mac Kenzie, W.R. \n(1997) Recurrent Chlamydial Infections Increase the Risks of Hospitalization for Ec-\ntopic Pregnancy and Pelvic Inflammatory Disease. American Journal of Obstetrics \nand Gynecology, 176, 103-107. https://doi.org/10.1016/s0002-9378(97)80020-8 \n[11] Taylor-Robinson, D. (1998) The Role of Ureaplasma Urealyticum . International \nJournal of STD & AIDS, 9, 123-124. \n[12] Brook, I. and Gober, A.E. (2005) Antimicrobial Resistance in the Nasopharyngeal \nFlora of Children with Acute Otitis Media and Otitis Media Recurring after Amoxi-\ncillin Therapy. Journal of Medical Microbiology, 54, 83-85.  \nhttps://doi.org/10.1099/jmm.0.45819-0 \n[13] Hellstrom, W.J.G., Schachter, J., Sweet, R.L. and Dale McClure, R. (1987) Is There a \nRole for \nChlamydia Trachomatis and Genital Mycoplasma in Male Infertility? Fertil-\nity and Sterility, 48, 337-339. https://doi.org/10.1016/s0015-0282(16)59370-4 \n[14] Imudia, A.N., Detti, L., Puscheck, E.E., Yelian, F.D. and Diamond, M.P. (2008) The \nPrevalence of \nUreaplasma Urealyticum, Mycoplasma Hominis, Chlamydia Tracho-\nmatis and Neisseria Gonorrhoeae Infections, and the Rubella Status of Patients Un-\ndergoing an Initial Infertility Evaluation. Journal of Assisted Reproduction and Ge-\nnetics, 25, 43-46. https://doi.org/10.1007/s10815-007-9192-z \n[15] Moini, A., Riazi, K., Amid, V., Ashrafi, M., Tehraninejad, E., Madani, T., et al. (2005) \nEndometriosis May Contribute to Oocyte Retrieval -Induced Pelvic Inflammatory \nDisease: Report of Eight Cases. Journal of Assisted Reproduction and Genetics , 22, \n307-309. https://doi.org/10.1007/s10815-005-6003-2 \n[16] Matysiak-Klose, D., Mankertz, A. and Holzmann, H. (2024) The Epidemiology and \nDiagnosis of Measles — Special Aspects Relating to Low Incidence. Deutsches Ärz-\nteblatt international, 121, 875-881. https://doi.org/10.3238/arztebl.m2024.0211 \n[17] Curty, G., de Carvalho, P.S. and Soares, M.A. (2019) The Role of the Cervicovaginal \nMicrobiome on the Genesis and as a Biomarker of Premalignant Cervical Intraepi-\nthelial Neoplasia and Invasive Cervical Cancer. \nInternational Journal of Molecular \nSciences, 21, Article 222. https://doi.org/10.3390/ijms21010222 \n[18] Lehtinen, M., Luukkaala, T., Wallin, K., Paavonen, J., Thoresen, S., Dillner, J., et al. \n(2001) Human Papillomavirus Infection, Risk for Subsequent Development of Cer-\nvical Neoplasia and Associated Population Attributable Fraction. Journal of Clinical \nVirology, 22, 117-124. https://doi.org/10.1016/s1386-6532(01)00172-x \n[19] Ravel, J., Gajer, P., Abdo, Z., Schneider, G.M., Koenig, S.S.K., McCulle, S.L., et al. \n\nZ. D. Wei, C. J. Yi \n \n \nDOI: 10.4236/jbm.2025.1311015 223 Journal of Biosciences and Medicines \n \n(2011) Vaginal Microbiome of Reproductive -Age Women. Proceedings of the Na-\ntional Academy of Sciences, 108, 4680-4687.  \nhttps://doi.org/10.1073/pnas.1002611107 \n[20] Renz, K.G., Cooke, J., Clarke, N., Cheetham, B.F., Hussain, Z., Fakhrul Islam, A.F.M., \net al. (2012) Pathotyping of Australian Isolates of Marek’s Disease Virus and Associ-\nation of Pathogenicity with Meq Gene Polymorphism. Avian Pathology, 41, 161-176.  \nhttps://doi.org/10.1080/03079457.2012.656077 \n[21] McCormack, W.M. (1994) Pelvic Inflammatory Disease. New England Journal of \nMedicine, 330, 115-119. https://doi.org/10.1056/nejm199401133300207 \n[22] Brunham, R.C., Martin, D.H., Kuo, C.C., Wang, S.P., Stevens, C.E., Hubbard, T., et \nal. (1981) Cellular Immune Response during Uncomplicated Genital Infection with \nChlamydia Trachomatis in Humans. Infection and Immunity, 34, 98-104.  \nhttps://doi.org/10.1128/iai.34.1.98-104.1981 \n[23] Beatty, W.L., Morrison, R.P. and Byrne, G.I. (1994) Persistent Chlamydiae: From Cell \nCulture to a Paradigm for Chlamydial Pathogenesis. Microbiological Reviews , 58, \n686-699. https://doi.org/10.1128/mr.58.4.686-699.1994 \n[24] Zhang, Q., Xing, X., Liu, S., Xie, X., Liu, X., Qian, F., et al. (2019) Intramural Ectopic \nPregnancy Following Pelvic Adhesion: Case Report and Literature Review. Archives \nof Gynecology and Obstetrics, 300, 1507-1520.  \nhttps://doi.org/10.1007/s00404-019-05379-3 \n[25] Pi, R., Liu, Y., Zhao, X., Liu, P. and Qi, X. (2020) Tubal Infertility and Pelvic Adhesion \nIncrease Risk of Heterotopic Pregnancy after \nin Vitro Fertilization: A Retrospective \nStudy. Medicine, 99, e23250. https://doi.org/10.1097/md.0000000000023250 \n[26] Oliveira Souza Lima, S.R., Kanemitsu, K., Rashid, M., Patel, V.K. and Ali, M. (2024) \nLong-term Efficacy and Safety of Adhesion Prevention Agents in Abdominal and Pel-\nvic Surgeries: A Systematic Review. \nCureus, 16, e71280.  \nhttps://doi.org/10.7759/cureus.71280 \n[27] Machado, A.C.S., Bandea, C.I., Alves, M.F.C., Joseph, K., Igietseme, J., Miranda, A.E., \net al. (2011) Distribution of Chlamydia Trachomatis Genovars among Youths and \nAdults in Brazil. Journal of Medical Microbiology, 60, 472-476.  \nhttps://doi.org/10.1099/jmm.0.026476-0 \n[28] Sehnem, L., Bodanese, L.C., Repetto, G. and Staub, H.L. (2010) Iga Antibodies to \nchlamydia Trachomatis and Metabolic Syndrome. Microbiology and Immunology , \n54, 747-749. https://doi.org/10.1111/j.1348-0421.2010.00281.x \n[29] Lorimer, K. and Hart, G.J. (2010) Knowledge of Chlamydia Trachomatis among Men \nand Women Approached to Participate in Community -Based Screening, Scotland, \nUk. BMC Public Health, 10, Article No. 794.  \nhttps://doi.org/10.1186/1471-2458-10-794 \n[30] Townsend, L.C., Stahlman, S.L., Escobar, J.D., Osuna, A.B., Casey, T.M., Winkler, \nE.L., \net al. (2024) Positivity and Follow -Up Testing of Chlamydia Trachomatis and \nNeisseria Gonorrhoeae Infections in Universally Screened Female Basic Military \nTrainees. Sexually Transmitted Diseases, 52, 176-180.  \nhttps://doi.org/10.1097/olq.0000000000002099 \n[31] Shen, L., Diggs, C., Ferdous, S., et al. (2024) The SWIB Domain -Containing DNA \nTopoisomerase I of Chlamydia Trachomatis Mediates DNA Relaxation. bioRxiv. \n[32] Khan, K.N., Fujishita, A., Kitajima, M., Ishimaru, T., Ogawa, K., Koshiba, A., et al. \n(2021) Decreased Occurrence of Endometriosis in Women with Chlamydia tracho-\nmatis Infection. American Journal of Reproductive Immunology, 86, e13498.  \nhttps://doi.org/10.1111/aji.13498 \n\nZ. D. Wei, C. J. Yi \n \n \nDOI: 10.4236/jbm.2025.1311015 224 Journal of Biosciences and Medicines \n \n[33] Gazvani, R., Coyne, L., Anttila, T., Saikku, P., Paavonen, J. and Templeton, A. (2011) \nAntibodies to Chlamydia trachomatisin Serum and Peritoneal Fluid of Women with \nEndometriosis. Human Fertility, 14, 64-67.  \nhttps://doi.org/10.3109/14647273.2010.548846 \n[34] Oppelt, P., Renner, S.P., Strick, R., Valletta, D., Mehlhorn, G., Fasching, P.A., et al. \n(2010) Correlation of High -Risk Human Papilloma Viruses but Not of Herpes Vi-\nruses or Chlamydia Trachomatis with Endometriosis Lesions. Fertility and Sterility, \n93, 1778-1786. https://doi.org/10.1016/j.fertnstert.2008.12.061 \n[35] Ross, P. (2021) Retraction: Ginsenoside Rf Alleviates Dysmenorrhea and Inflamma-\ntion through the BDNF-TrkB-CREB Pathway in a Rat Model of Endometriosis. Food \n& Function, 12, 5187. https://doi.org/10.1039/d1fo90040d \n[36] Wu, M. and Zhang, Y. (2021) MiR -182 Inhibits Proliferation, Migration, Invasion \nand Inflammation of Endometrial Stromal Cells through Deactivation of NF-κB Sig-\nnaling Pathway in Endometriosis. Molecular and Cellular Biochemistry , 476, 1575-\n1588. https://doi.org/10.1007/s11010-020-03986-2 \n[37] Sekulovski, N., Whorton, A.E., Tanaka, T., Hirota, Y., Shi, M., MacLean, J.A., et al. \n(2020) Niclosamide Suppresses Macrophage-Induced Inflammation in Endometrio-\nsis. Biology of Reproduction, 102, 1011-1019.  \nhttps://doi.org/10.1093/biolre/ioaa010 \n[38] MacSharry, J., Kovács, Z., Xie, Y., Adamczyk, B., Walsh, C., Reidy, F., et al. (2024) \nEndometriosis Specific Vaginal Microbiota Links to Urine and Serum N -Glycome. \nScientific Reports, 14, Article No. 25372.  \nhttps://doi.org/10.1038/s41598-024-76125-2 \n[39] Qing, X., Xie, M., Liu, P., Feng, O., Leng, H., Guo, H., et al. (2024) Correlation be-\ntween Dysbiosis of Vaginal Microecology and Endometriosis: A Systematic Review \nand Meta-Analysis. \nPLOS ONE, 19, e0306780.  \nhttps://doi.org/10.1371/journal.pone.0306780 \n[40] Lu, F., Wei, J., Zhong, Y., Feng, Y., Ma, B., Xiong, Y., et al. (2022) Antibiotic Therapy \nand Vaginal Microbiota Transplantation Reduce Endometriosis Disease Progression \nin Female Mice via NF -κB Signaling Pathway. \nFrontiers in Medicine, 9, Article ID: \n831115. https://doi.org/10.3389/fmed.2022.831115 \n[41] Fan, Y., Chen, H., Chen, W., Liu, Y., Fu, Y. and Wang, L. (2018) Expression of In-\nflammatory Cytokines in Serum and Peritoneal Fluid from Patients with Different \nStages of Endometriosis. \nGynecological Endocrinology, 34, 507-512.  \nhttps://doi.org/10.1080/09513590.2017.1409717 \n[42] Drugan, T., Malutan, A., Ciortea, R., Mocan-Hognogi, R., Bucuri, C., Rada, M., et al. \n(2015) Serum Anti-Inflammatory Cytokines for the Evaluation of Inflammatory Sta-\ntus in Endometriosis. Journal of Research in Medical Sciences, 20, 668-674.  \nhttps://doi.org/10.4103/1735-1995.166215 \n[43] Wu, M. and Ho, H. (2003) The Role of Cytokines in Endometriosis. American Jour-\nnal of Reproductive Immunology, 49, 285-296.  \nhttps://doi.org/10.1034/j.1600-0897.2003.01207.x \n[44] Silva, B.N., Fernandes, N., Carvalho, L., et al. (2023) Lactic Acid Bacteria from Arti-\nsanal Raw Goat Milk Cheeses: Technological Properties and Antimicrobial Potential. \nItalian Journal of Food Safety, 12, Article 11559. \n[45] Grande, G., Vincenzoni, F., Milardi, D., Pompa, G., Ricciardi, D., Fruscella, E., et al. \n(2017) Cervical Mucus Proteome in Endometriosis. Clinical Proteomics, 14, Article \nNo. 7. https://doi.org/10.1186/s12014-017-9142-4 \n\nZ. D. Wei, C. J. Yi \n \n \nDOI: 10.4236/jbm.2025.1311015 225 Journal of Biosciences and Medicines \n \n[46] Lin, Y., Chen, Y., Chang, H., Au, H., Tzeng, C. and Huang, Y. (2018) Chronic Niche \nInflammation in Endometriosis -Associated Infertility: Current Understanding and \nFuture Therapeutic Strategies. International Journal of Molecular Sciences, 19, Arti-\ncle 2385. https://doi.org/10.3390/ijms19082385 \n[47] Peipert, J.F., Ness, R.B., Blume, J., Soper, D.E., Holley, R., Randall, H., et al. (2001) \nClinical Predictors of Endometritis in Women with Symptoms and Signs of Pelvic \nInflammatory Disease. \nAmerican Journal of Obstetrics and Gynecology , 184, 856-\n864. https://doi.org/10.1067/mob.2001.113847 \n[48] Zhou, W., Yang, H., Shao, J., Mei, J., Chang, K., Zhu, R., et al. (2019) Anti-Inflamma-\ntory Cytokines in Endometriosis. Cellular and Molecular Life Sciences , 76, 2111-\n2132. https://doi.org/10.1007/s00018-019-03056-x \n[49] Malutan, A.M., Drugan, T., Costin, N., Ciortea, R., Bucuri, C., Rada, M.P., et al.  \n(2015) Clinical Immunology Pro-Inflammatory Cytokines for Evaluation of Inflam-\nmatory Status in Endometriosis. Central European Journal of Immunology , 1, 96-\n102. https://doi.org/10.5114/ceji.2015.50840 \n[50] Liang, Y., Zhao, C., Wen, Y., Sheng, D., Wei, T., Hu, T., et al. (2024) Modulation of \nLocal Immunity by the Vaginal Microbiome Is Associated with Triggering Spontane-\nous Preterm Birth. Frontiers in Immunology, 15, Article ID: 1481611.  \nhttps://doi.org/10.3389/fimmu.2024.1481611 \n[51] Li, J., Zhu, Y., Mi, J., Zhao, Y., Holyoak, G.R., Yi, Z., et al. (2022) Endometrial and \nVaginal Microbiome in Donkeys with and without Clinical Endometritis. Frontiers \nin Microbiology, 13, Article ID: 884574. https://doi.org/10.3389/fmicb.2022.884574 \n[52] Dolmans, M. and Donnez, J. (2022) Emerging Drug Targets for Endometriosis. Bio-\nmolecules, 12, Article 1654. https://doi.org/10.3390/biom12111654 \n[53] Guo, C. and Zhang, C. (2024) Role of the Gut Microbiota in the Pathogenesis of En-\ndometriosis: A Review. Frontiers in Microbiology, 15, Article ID: 1363455.  \nhttps://doi.org/10.3389/fmicb.2024.1363455","source_license":"CC0","license_restricted":false}