Reproductive Sciences最新文献

{"title":"Deciphering the Role of ZEB1 as a Central Regulator of Epithelial-Mesenchymal Transition and Hormonal Resistance in Endometriosis.","authors":"Sanket Shirodkar, Gaurav Doshi","doi":"10.1007/s43032-026-02181-w","DOIUrl":"10.1007/s43032-026-02181-w","url":null,"abstract":"<p><p>Endometriosis is a chronic inflammatory and sex steroid hormone-dependent gynaecologic disease, characterised by endometrial cell proliferation outside the uterine cavity, often accompanied by fibrosis, progesterone resistance, and high recurrence despite hormonal and surgical interventions. Epithelial-mesenchymal transition (EMT) is important for establishment of lesions and invasiveness, but the upstream transcriptional regulators that integrate hormonal, inflammatory and epigenetic signals are incompletely defined. This review emphasises ZEB1 as a molecular integrator at the systems level in endometriosis pathogenesis. We reviewed evidence for selective upregulation of ZEB1 in ectopic lesions, where it inhibits epithelial adhesion molecules, stabilises mesenchymal differentiation and activates the attachment-invasion angiogenesis cascade required for lesion persistence. In addition to EMT, we discuss bidirectional crosstalk between ZEB1 and endocrine signalling, illustrating how oestrogen-mediated induction and suppression of progesterone receptor pathways converge to establish progesterone resistance. The review includes miR-200 family members, long non-coding RNAs and circular RNAs that strengthen ZEB1 expression through multilayered feedback mechanisms that perpetuate chronic inflammatory and pro-fibrotic microenvironments. Critically, it tackles translational complexity by incorporating the heterogeneity of lesions uncovered through single-cell and spatial transcriptomics, and by assessing the experimental models necessary to determine causal relevance. Additionally, it addresses the paradox of targeting ZEB1 therapeutically, considering its physiological function in endometrial regeneration and implantation. Understanding the oestrogen-ZEB1-TGF-β axis is critical for developing mechanism-based precision interventions for endometriosis.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1954-1977"},"PeriodicalIF":2.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Endocannabinoid System in Endometriosis-Associated Pain: Mechanisms, Molecular Targets, and Therapeutic Implications.","authors":"Alexandra M Stone, Vanessa L Veltre, Olivia G Camp, Mia M Biernat, Husam M Abu-Soud","doi":"10.1007/s43032-026-02201-9","DOIUrl":"10.1007/s43032-026-02201-9","url":null,"abstract":"<p><p>Endometriosis is a chronic gynecological disorder affecting approximately 10% of reproductive-age women, characterized by the ectopic growth of endometrial tissue and severe pain, including dysmenorrhea, chronic pelvic pain, dyspareunia, dysuria, and dyschezia. Current treatments are limited in efficacy and associated with significant side effects, underscoring the urgent need for novel therapeutic strategies. The endocannabinoid system (ECS) has emerged as a promising therapeutic target, given its well-established roles in pain modulation, inflammation, and immune regulation. Epidemiological evidence demonstrates that women with endometriosis increasingly use cannabis for symptom self-management, yet the underlying mechanisms remain poorly characterized. This review integrates preclinical and human evidence to comprehensively evaluate the mechanistic basis of cannabinoid efficacy in endometriosis-associated pain. Evidence from in vitro studies and animal models indicates that cannabinoids target three main mechanisms of endometriosis-associated pain, including inflammation, nociceptive signaling, and lesion proliferation. Cannabinoids suppress pain signaling and sensitization by interacting with cannabinoid and non-cannabinoid receptors expressed in endometriotic lesions. Cannabinoids attenuate endometriosis-induced inflammation by inhibiting proinflammatory cytokine signaling and reducing the release of inflammatory mediators by mast cells and peritoneal macrophages. Cannabinoids also exert antiproliferative effects in endometriosis models, thereby suppressing the growth of endometriotic lesions. In conclusion, the ECS is a promising therapeutic target for endometriosis-associated pain, as it regulates nociception, inflammation, and proliferation. These promising findings highlight the potential therapeutic benefits of cannabinoids for endometriosis-associated pain, warranting the need for clinical trials to evaluate the safety and effectiveness of cannabinoid therapies in endometriosis.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1891-1906"},"PeriodicalIF":2.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatics, Machine Learning and Functional Validation Reveal Mitophagy-Related FABP5 and HMOX1 as Diagnostic and Therapeutic Targets in Polycystic Ovary Syndrome.","authors":"Aiqin Lian, Yuxin Li, Weijun He, Xinjian Luo, Long Jin, Chaohui Li","doi":"10.1007/s43032-026-02156-x","DOIUrl":"10.1007/s43032-026-02156-x","url":null,"abstract":"<p><p>Polycystic Ovary Syndrome (PCOS) is a heterogeneous endocrine-metabolic disorder characterized by ovulatory dysfunction, hyperandrogenism, and insulin resistance, in which mitochondrial dysfunction has been increasingly implicated. Mitochondria regulate energy metabolism and oxidative stress, with mitophagy maintaining cellular balance. Dysregulated mitophagy relates to PCOS metabolic issues like obesity and inflammation. This study analyzed gene expression datasets to find autophagy-related genes in PCOS, identifying AMFR, FABP5, and HMOX1 as key genes. We built a diagnostic model and confirmed their elevated expression in a hyperandrogenism-induced PCOS cell model, revealing potential small-molecule drugs targeting these genes. Our integrative bioinformatics analysis and systematic molecular experiments suggest that FABP5 and HMOX1 are potential PCOS diagnostic targets, with high-affinity compounds as therapies,highlighting the pathological relevance of mitophagy-related genes in PCOS.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2018-2036"},"PeriodicalIF":2.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beclin1 Regulates Sertoli Cell Function to Maintain Mouse Spermatogenesis.","authors":"Yuqing Cai, Wanzhen Li, Yifeilong He, Zhifeng Zhao, Xinyi Lin, Jing Wang, Yuchuan Luo, Yinghe Qin, Yingjie Wu","doi":"10.1007/s43032-026-02202-8","DOIUrl":"10.1007/s43032-026-02202-8","url":null,"abstract":"<p><p>Besides providing nutrients, Sertoli cells support spermatogenic cells development by maintaining seminiferous epithelial polarity, forming the blood-testis barrier (BTB), and phagocytosing residual bodies. Beclin1, a core component of the autophagy initiation complex, is critical for autophagic flux in many cell types. However, its role in Sertoli cells remains unclear. Here, we generated a Sertoli cell-specific Becn1 knockout (cKO) mouse model and found that 9-week-old male cKO mice exhibited reduced fertility with decreased sperm quality and vacuolated seminiferous tubules, and became completely infertile by 12 weeks of age. These defects were associated with disrupted BTB integrity and reduced expression of Claudin-11 in the testes. Further analysis revealed that loss of Beclin1led to impaired autophagosome formation, evidenced by reduced LC3-II/LC3-I ratio. In summary, these findings demonstrate that Beclin1 in Sertoli cells is vital for spermatogenesis and male fertility.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2068-2080"},"PeriodicalIF":2.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149031042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of Early Pregnancy Loss: Reproductive Outcome in Subsequent Euploid Embryo Transfers.","authors":"Emily A Clarke, Sarah C Roger, Raina Kishan, Morgan Baird, Joseph A Lee, Eric Flisser, Tanmoy Mukherjee, Alan B Copperman","doi":"10.1007/s43032-026-02200-w","DOIUrl":"10.1007/s43032-026-02200-w","url":null,"abstract":"<p><p>Early pregnancy loss (EPL) is commonly managed with medical or surgical intervention, with comparable outcomes described in the general population. However, intrauterine instrumentation including dilation and curettage has been linked to endometrial thinning, associated with inferior in vitro fertilization (IVF) outcomes. Limited data exists on how EPL management influences subsequent IVF outcomes, particular in patients undergoing single euploid embryo transfer (SEET). This single-center, retrospective cohort study compared endometrial thickness and outcomes in the subsequent SEET cycle between patients with EPL who underwent either medical or surgical management. A total of 203 patients were included: 88 patients who underwent medical and 115 who underwent surgical management. The primary outcome was change in endometrial thickness between the initial and subsequent SEET cycle. Secondary outcomes included SEET cycle cancellation due to thin endometrium (< 7 mm) and subsequent SEET outcomes. Between the initial and subsequent SEET cycle, change in endometrial thickness was similar between groups (Medical + 0.3 ± 1.4 mm, Surgical + 0.1 ± 1.5 mm; P = 0.65). Endometrial thickness in the subsequent cycle was also comparable (Medical 9.4 ± 1.5 mm, Surgical 9.1 ± 1.2 mm; P = 0.20). SEET cycle cancellation due to thin endometrium was low and similar between groups (Medical 3.4% [95% CI 1.0-9.6] (n = 3), Surgical 2.6% [95% CI 1.0-7.4] (n = 3); P = 0.74). While surgical management was associated with higher subsequent clinical pregnancy loss (15.7% vs. 4.9%; P < 0.05; aOR 3.72 [95% CI 1.11-12.47]), subsequent live birth rates were similar between groups (Medical 48.8%, Surgical 40.7%; P = 0.27; aOR 0.67 [95% CI 0.35-1.28]). These findings may help guide counseling patients undergoing IVF regarding management decision-making when facing EPL.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2148-2154"},"PeriodicalIF":2.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning and Functional Analysis of Placental DNA Methylation Signatures for Early-Onset Preeclampsia.","authors":"Raunak Sharda, Valentina L Kouznetsova, Igor F Tsigelny","doi":"10.1007/s43032-026-02183-8","DOIUrl":"10.1007/s43032-026-02183-8","url":null,"abstract":"<p><p>Early-onset preeclampsia (EOPE) is a pregnancy disorder characterized by abnormal placental development and substantial maternal and fetal risk. DNA methylation at CpG sites has emerged as a key epigenetic mechanism in EOPE. In this study, we developed machine learning models for EOPE classification using β-values from CpG sites in placental tissue. Starting from 599 EOPE-associated CpG sites reported earlier, we used attribute selection in WEKA to identify 30 statistically significant descriptors, which mapped to 19 unique genes. Multiple classifiers were trained and evaluated, and the SPegasos classifier demonstrated the best performance, achieving 95.45% accuracy and an area under the receiver operating characteristic curve of 0.9545 in tenfold cross‑validation, and 95% accuracy in an independent validation dataset. These findings suggest a potentially high correlation between the CpG methylation signatures and EOPE. By creating a machine learning model, we can potentially classify a sample as having EOPE or a normal pregnancy using DNA methylation data at specific CpG sites in placental tissue. Furthermore, we identified the adipogenesis pathway to be central to the disease's pathophysiology. Gain ratio analysis highlighted a subset of CpG sites with particularly strong discriminative power between EOPE and control placentas. Functional annotation of the 19 CpG‑associated genes using protein and pathway enrichment analyses revealed enrichment in signal transduction, steroid and lipid metabolism, and cell developmental processes. Pathway analysis identified adipogenesis as a central pathway, consistent with dysregulated adipokine signaling and systemic inflammation in EOPE. These findings demonstrate that placental CpG methylation signatures can accurately distinguish EOPE from normal pregnancies and provide mechanistic insight into disrupted adipogenesis‑related pathways. The identified CpG methylation signature may serve as a basis for developing early molecular biomarkers and targeted strategies to improve EOPE diagnosis and management.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2094-2108"},"PeriodicalIF":2.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Profiling of IgG and IgA Glycosylation in Pregnancy Reveals Early Associations with BMI, Nulliparity and Conception Mode: The Rotterdam Periconception Cohort.","authors":"Lotte W Voskamp, Anna Daniels, Melek Rousian, Mandy van Hoek, Manfred Wuhrer, Régine P M Steegers-Theunissen, A H Jan Danser, Koen Verdonk","doi":"10.1007/s43032-026-02190-9","DOIUrl":"10.1007/s43032-026-02190-9","url":null,"abstract":"<p><p>During early pregnancy, the maternal immune system recalibrates to tolerate the semi-allogeneic fetus. Immunoglobulin (Ig) function is modulated by glycosylation. Prior studies showed increases in anti-inflammatory glycosylation traits (galactosylation and sialylation) in IgG and to a lesser extent in IgA towards the third trimester. This study aimed to characterize IgG and IgA glycosylation patterns throughout pregnancy and assess associations with maternal age, gravidity, body mass index (BMI) and conception mode. In the Rotterdam Periconception Cohort, serum samples from 202 women with singleton pregnancies were collected at 9, 11, 13, 22, and 32 weeks'' gestation. IgG and IgA glycopeptides were analyzed using validated liquid chromatography-mass spectrometry and summarized into galactosylation, sialylation, fucosylation, and bisection traits. Longitudinal changes were assessed with linear mixed-effects models and FDR correction and associations with maternal factors were derived from model estimates. Already in the first trimester, galactosylation and sialylation increased and bisection decreased for both IgG and IgA. IgG galactosylation and sialylation continued rising throughout pregnancy, whereas most IgA traits reversed after the first trimester. Higher BMI was associated with a pro-inflammatory profile (lower IgG galactosylation; higher IgG and IgA fucosylation). Assisted reproduction and nulliparity were associated with anti-inflammatory changes, including higher galactosylation and sialylation. In conclusion, IgG and IgA glycosylation shifts towards an anti-inflammatory profile as early as the first trimester, potentially promoting immune tolerance. Pro-inflammatory changes with higher BMI, and distinct profiles in nulliparous and ART pregnancies, may represent biological pathways linking maternal factors to pregnancy outcomes, supporting glycosylation as a candidate biomarker.Trial registration number: This study is registered at the Dutch Trial Register (NTR6854).</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2081-2093"},"PeriodicalIF":2.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13645990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin in Pregnancy-Related Disorders: A Review of Protective Mechanisms and Therapeutic Potential.","authors":"Shanza Waseem, Jun Zhan, Lei Yu, Xue Xiao","doi":"10.1007/s43032-026-02196-3","DOIUrl":"10.1007/s43032-026-02196-3","url":null,"abstract":"<p><p>Melatonin (N-acetyl-5-methoxytryptamine), classically known as a pineal neurohormone regulating circadian rhythms, has emerged as a critical pleiotropic molecule in reproductive physiology. Beyond its role in establishing circadian entrainment, it acts as a potent antioxidant, anti-inflammatory agent, and mitochondrial function modulator. This review synthesizes current knowledge on the multifaceted roles of melatonin in normal pregnancy and its pathophysiological implications in major gestational disorders, including preeclampsia (PE), fetal growth restriction (FGR), gestational diabetes mellitus (GDM), and preterm birth (PTB). Distinct from prior reviews, this work provides a structured, disorder-specific analysis of translational evidence with a critical evaluation of pharmacological optimization strategies, biomarker-driven trial design, and long-term developmental safety considerations. We highlight the dual source of melatonin maternal and placental and its receptor-mediated and receptor-independent actions. Compelling preclinical data and emerging clinical studies suggest that melatonin supplementation may represent a novel, safe, and effective therapeutic strategy for mitigating oxidative stress and inflammation at the maternal-fetal interface. This article reviews the mechanistic underpinnings, summarizes existing evidence in a structured format, and identifies critical gaps for future translational research.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1978-1990"},"PeriodicalIF":2.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obstetric and Neonatal Outcomes in Deep Infiltrating Versus Superficial Endometriosis: A Retrospective Cohort Study.","authors":"İsmail Baglar, Tamer Topaloglu, Esra Keles, Aylin Yılmaz, Sule Yildirim Kopuk, Buket Yigit Civi, Khayala Alakbarli Guliyeva, Ece Nokay, Mehmet Karahan, Dilanur Agir","doi":"10.1007/s43032-026-02215-3","DOIUrl":"10.1007/s43032-026-02215-3","url":null,"abstract":"<p><p>To compare obstetric and neonatal outcomes between women with surgically confirmed deep infiltrating endometriosis (DIE) and superficial endometriosis, focusing on lesion-specific risk profiles. This retrospective cohort study included women with surgically confirmed endometriosis who achieved singleton pregnancies at a tertiary referral center between 2015 and 2024. Patients were classified as having deep infiltrating or superficial endometriosis. Obstetric and neonatal outcomes were obtained from medical records. Primary outcomes were placenta previa and preterm birth before 37 gestational weeks. Secondary outcomes included placenta-related complications, maternal perinatal outcomes, and neonatal morbidity. Multivariable logistic regression analyses were performed adjusting for maternal age, pre-pregnancy body mass index, parity, assisted reproductive technology use, adenomyosis, and previous uterine surgery. A total of 268 pregnancies were analyzed (102 DIE, 166 superficial endometriosis). Placenta previa was significantly more frequent in the DIE group and remained independently associated after adjustment (adjusted odds ratio 2.41, 95% confidence interval 1.02-5.68). Preterm birth was more common among women with DIE, but this association did not remain significant. A placenta-related composite outcome, including placenta previa and placental abruption, was independently associated with DIE. Neonatal intensive care unit admission was also more frequent in the DIE group and remained independently associated (adjusted odds ratio 1.89, 95% confidence interval 1.01-3.54). Deep infiltrating endometriosis is associated with higher risks of placenta-related complications and adverse neonatal outcomes compared with superficial endometriosis. Lesion-based phenotyping may support clinically relevant perinatal risk stratification in pregnancies complicated by endometriosis.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2010-2017"},"PeriodicalIF":2.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Biological Disease-Staging Model of Polyendocrine Metabolic Ovarian Syndrome: From Plasticity-Dominant States to Pathological Remodeling.","authors":"Hiroshi Kobayashi","doi":"10.1007/s43032-026-02191-8","DOIUrl":"10.1007/s43032-026-02191-8","url":null,"abstract":"<p><p>Polyendocrine metabolic ovarian syndrome (PMOS) is a heterogeneous endocrine-metabolic disorder characterized by reproductive dysfunction, metabolic abnormalities, and hormonal dysregulation. Although the Rotterdam criteria are widely used for phenotypic classification, accumulating evidence suggests that disease heterogeneity reflects varying contributions of insulin resistance, hyperandrogenism, chronic inflammation, mitochondrial dysfunction, autophagy dysregulation, and cellular senescence. To review the role of integrated intracellular signaling networks in PMOS and propose a conceptual model that explains disease progression and heterogeneity. A narrative review of studies published through December 2025 was conducted, focusing on insulin resistance, androgen excess, inflammation, autophagy, mitochondrial dysfunction, cellular senescence, and reproductive dysfunction. The present review proposes a three-stage disease spectrum consisting of a plasticity-dominant state, an adaptive-transition state, and a pathological-remodeling state. The plasticity-dominant state is characterized by preserved tissue adaptability despite metabolic and endocrine abnormalities. The adaptive-transition state involves persistent signaling dysregulation accompanied by impaired autophagy and mitochondrial dysfunction. In the pathological-remodeling state, cellular senescence, senescence-associated secretory phenotype (SASP)-driven inflammation, fibrosis, and tissue remodeling become increasingly prominent, resulting in reduced tissue plasticity and sustained disease maintenance. In conclusion, PMOS may be better understood as a dynamic pathophysiological spectrum rather than a static disorder. This model integrates metabolic dysfunction, inflammation, mitochondrial impairment, cellular senescence, and tissue remodeling, providing a complementary framework to the Rotterdam classification and a potential basis for improved disease stratification and personalized therapeutic strategies.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1931-1953"},"PeriodicalIF":2.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}