Reproductive Sciences最新文献

{"title":"The Gut-Insulin Axis in Polycystic Ovary Syndrome: A Narrative Review of Gut Dysbiosis, Inflammation, and Emerging Therapeutic Strategies.","authors":"Shruti, Kanchan Bala","doi":"10.1007/s43032-026-02220-6","DOIUrl":"https://doi.org/10.1007/s43032-026-02220-6","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a complicated, endocrine-endemic disorder with a prevalence rate of 8-13% in reproductive-age women in the world, which manifests through insulin resistance, hyperandrogenism, and reproductive dysfunction. Despite its high global prevalence, existing therapeutic interventions focus predominantly on symptom management rather than targeting the heterogeneous and multifactorial pathophysiology of the syndrome. Intestinal barrier integrity is destroyed by dysbiosis of the gut microbiota and induces endotoxemia and chronic low-grade inflammation through signalling pathways, such as LPS-TLR4-NF-kB signalling, which contribute to increased insulin resistance and androgen excess. These mechanistic pathways we dissect include changes in short-chain fatty acids (SCFAs), bile acid metabolism, involvement of FXR and TGR5 receptors, neuroendocrine regulation of the gut-brain axis, and microbial metabolites (tryptophan and agmatine), which altogether alter metabolic and reproductive abnormalities in PCOS. The preclinical evidence in the area of fecal microbiota transplantation proves the causal component of microbiota imbalance in the phenotype of PCOS. Dietary interventions that have been reviewed are fiber and resistant starch modulation, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and pharmacotherapies like metformin, which also alter the microbiome. They are heading towards individualized microbiome-based therapies and diagnostics, aided by artificial intelligence and standardized biomarkers. This review explains the emerging role of the gut-insulin axis as an important factor in the pathogenesis of PCOS and uses a novel way of combining them as a radical intervention for personalized and innovative PCOS treatment, which has the potential to enhance metabolic and endocrine health, as well as reproductive outcomes.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128455","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":"Stromal Remodeling and Collagen Dynamics under Antifibrotic Conditions in the Rat Prostate.","authors":"Luiz Roberto Falleiros Junior, Thalles Fernando Rocha Ruiz, Vitor Grigio, Stella Bicalho-Silva, Simone Jacovaci Colleta, Lorena Gabriela de Souza, Luara Jesus Ferrato, Patrícia Simone Leite Vilamaior, Thiago da Silveira Antoniassi, Luís César Fava Spessoto, Sebastião Roberto Taboga, Fernando Nestor Facio Junior","doi":"10.1007/s43032-026-02221-5","DOIUrl":"https://doi.org/10.1007/s43032-026-02221-5","url":null,"abstract":"<p><p>The prostate is a hormone-sensitive gland, in which stromal composition is important for epithelial regulation. Fibrotic alterations in the stroma may enhance epithelial imbalance and pre-neoplastic lesions. The purpose of this study was to assess the time-dependent antifibrotic effects of mycophenolate mofetil (MMF) in rat prostate. Male Wistar rats were treated with MMF for 7 or 30 days, and prostate samples were histologically and immunohistochemically examined. Stromal fiber content, hormone receptor expression, and immune cell incidence were analyzed. Collagen III and elastin fibers decreased at 7 days, with increased matrix metalloproteinases 2 expression and reduced androgen receptor in the epithelium, resulting in decreased proliferation and enhanced apoptosis. Collagen I breakdown at 30 days was associated with increased matrix metalloproteinases 13 and reduced smooth muscle area, with increased non-muscular stroma and vascular density. Degranulated mast cells were increased early on, and macrophages at 30 days, reflecting their successive involvement in stromal remodeling. These findings define two time windows of MMF-induced remodeling: initial extracellular matrix disassembly with epithelial influence, and later structural reorganization with vascular and immune components. This study provides relevant information about MMF as a potential tool for the study of antifibrotic response and stroma-epithelium interactions in androgen-dependent organs.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128457","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":"Identification of Ywhab as a Candidate Downstream Target of Figla During Ovarian Reserve Establishment.","authors":"Le Yang, Linshuang Li, Lin Shen, Hanwang Zhang","doi":"10.1007/s43032-026-02173-w","DOIUrl":"https://doi.org/10.1007/s43032-026-02173-w","url":null,"abstract":"<p><p>Early follicular development and primordial follicle formation are essential for ovarian reserve establishment, and disruption of this process may contribute to fertility disorders such as premature ovarian insufficiency (POI). Figla is an oocyte-specific transcription factor required for primordial follicle formation, but its candidate downstream genes and associated pathways remain incompletely understood. This study aimed to investigate the role of Figla in early follicular development and to explore its potential downstream regulatory events. A Figla knockout mouse model was generated to evaluate the effects of Figla deficiency on ovarian development and primordial follicle formation. ChIP-seq, motif analysis, and promoter activity assays were performed to identify FIGLA-associated chromatin regions and candidate genes. In addition, Figla overexpression and Ywhab knockdown experiments were conducted in a granulosa cell line, together with ovarian tissue Western blot analysis, to assess changes in growth activity, migration, ERK phosphorylation, and apoptosis-related markers. Figla was highly expressed in late embryonic and early postnatal ovaries, and its deletion primarily disrupted perinatal primordial follicle assembly, accompanied by progressive oocyte loss. ChIP-seq, motif, and promoter analyses supported Ywhab as a candidate gene potentially regulated by Figla. In KGN cells, Figla overexpression increased Ywhab expression and coincided with greater growth activity, migration, ERK phosphorylation, and changes in BAD/BCL-2/BAX-related markers. These cellular and signaling changes were attenuated by Ywhab knockdown. Additional ovarian tissue analysis showed reduced p-ERK/ERK and increased p-BAD/BAD ratios in Figla(-/-) ovaries. These findings support Ywhab as a candidate downstream gene potentially regulated by Figla and suggest a possible link between Figla-associated transcriptional regulation and cellular processes relevant to early follicular development. Further validation is needed before extending these findings to ovarian reserve establishment more broadly or to POI-related reproductive disorders.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113887","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 Autophagic Interaction Between p97/VCP and ABP Protein Expressions in Sertoli Cell Line: the Effects of Chloroquine and Rapamycin.","authors":"Ilkay Corumluoglu, Sevil Cayli","doi":"10.1007/s43032-026-02231-3","DOIUrl":"https://doi.org/10.1007/s43032-026-02231-3","url":null,"abstract":"<p><p>Sertoli cells play a pivotal role in spermatogenesis by providing structural support and delivering essential nutrients and signaling molecules to developing germ cells. A key function of these cells is the regulation of androgen-binding protein (ABP), which maintains the high intratesticular testosterone levels necessary for proper spermatogenic progression. Despite the critical nature of ABP, the mechanisms underlying its degradation within Sertoli cells remain poorly understood. This study investigates the role of the valosin-containing protein (p97/VCP) in the autophagic degradation of ABP, with a particular focus on molecular pathways that may contribute to male infertility and testicular dysfunction. Sertoli 15P-1 cells were treated with testosterone, chloroquine, and rapamycin, and subjected to single and double immunofluorescence staining, Western blotting, and siRNA-mediated knockdown experiments to explore the interaction between p97/VCP and ABP. Western blot analysis demonstrated that p62 expression was highest in the chloroquine + testosterone (CQ + T) group compared to control siRNA (Csi), although not statistically significant (p > 0.05). LC3 expression peaked in the chloroquine (CQ) group (p > 0.05). As expected, the lowest expression of p97/VCP was detected in the VCPsi group following siRNA transfection. Immunofluorescence analyses revealed significant differences in protein colocalization patterns across all treatment groups, except for p62 in rapamycin-treated samples. These findings provide the first evidence in the literature of a direct relationship between p97/VCP and ABP within Sertoli cells, underscoring the relevance of autophagic pathways in the regulation of male reproductive hormones. The data suggest a novel regulatory mechanism by which p97/VCP may influence spermatogenesis and male fertility through ABP degradation. Furthermore, this work lays a foundational framework for future investigations in other ABP-expressing tissues such as the brain, liver, and placenta, potentially linking p97/VCP expression to ABP-associated endocrine and pathophysiological disorders beyond the testis.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114033","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":"Targeting the Nicotine-driven Maladaptive ER Stress Axis: Protective Roles of Melatonin and Coenzyme Q10 in Rat Testis.","authors":"Aysel Eraslan Sakar, Cengiz Yildiz, Nurdan Coskun, Seydi Ahmet Sengul, Filiz Kazak Akcakavak, Tuncer Kutlu, Meryem Sayan, Derya Karabulut","doi":"10.1007/s43032-026-02235-z","DOIUrl":"https://doi.org/10.1007/s43032-026-02235-z","url":null,"abstract":"<p><p>The endoplasmic reticulum (ER) plays a pivotal role in protein folding and cellular homeostasis and is highly sensitive to oxidative stress. Nicotine is a potent pro-oxidant; however, its effects on ER stress signaling in testicular tissue and the protective potential of melatonin and coenzyme Q10 (CoQ10) remain insufficiently defined. This study investigated nicotine-induced sperm dysfunction and the involvement of oxidative stress-mediated ER stress pathways in rat testes. Two-month-old male Wistar albino rats (n = 48) were assigned to control, nicotine, nicotine + melatonin, nicotine + CoQ10, nicotine + melatonin + CoQ10, and melatonin + CoQ10 groups. Sperm quality was evaluated, and testicular tissue was analyzed for oxidative stress markers, ER stress-related gene expression, histopathological alterations, and immunohistochemical localization of proteins. Nicotine exposure significantly impaired sperm motility and membrane integrity and increased abnormal morphology, mortality, and apoptosis (p < 0.001). These effects were associated with elevated lipid peroxidation and depletion of antioxidant defenses, including reduced glutathione, glutathione peroxidase, and catalase (p < 0.001). Melatonin and/or CoQ10 partially restored sperm quality and antioxidant capacity. Moreover, antioxidant treatment significantly downregulated ER stress-associated genes (Activating transcription factor 4-ATF4; Activating transcription factor 6-ATF6; C/EBP homologous protein-CHOP; 78 kDa glucose-regulated protein-GRP78; inositol-requiring enzyme 1 alpha-IRE1α; and protein kinase RNA-like endoplasmic reticulum kinase-PERK) and reduced CHOP immunoreactivity, while CoQ10 selectively enhanced XBP-1 immunoreactivity. In conclusion, nicotine-induced testicular dysfunction is mediated by oxidative stress-driven ER stress activation, whereas melatonin and CoQ10 confer protection through modulation of redox balance and ER stress signaling.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114060","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":"3D Placental Bed Perfusion Ultrasound: Development and Internal Validation of Trimester-Specific Prediction Models for Early- and Late-Onset Preeclampsia.","authors":"Ming Liu, Zongqi Zhou, Jing Li, Hongling Wang, Leilei Yu, Chaoyi Qi, Huifeng Wang","doi":"10.1007/s43032-026-02234-0","DOIUrl":"https://doi.org/10.1007/s43032-026-02234-0","url":null,"abstract":"<p><p>This study aimed to develop trimester-specific and combined prediction models for early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) based on maternal clinical characteristics, uterine artery pulsatility index (UtA-PI), and 3D placental parameters, identify the optimal models, and construct static nomograms. A total of 1602 singleton pregnant women were prospectively enrolled from October 8, 2020 to May 31, 2025. All maternal clinical data were collected and participants were followed up until delivery. UtA-PI and 3D placental ultrasound parameters, including placental volume (PV), placental quotient (PQ), and placental blood flow vascularization index (PBVFI), were measured at 11-14 and 15-18 weeks of gestation, and the placental vascular growth rate (PVGR) was calculated. According to the gestational age at preeclampsia onset, participants were divided into the EOPE group (n = 29), LOPE group (n = 58), and normal control group (n = 1515). Univariable and multivariable Firth's logistic regression analyses were performed to identify independent predictors. Model performance was evaluated using receiver operating characteristic (ROC) curves, bootstrap-based calibration and decision curve analysis (DCA). Static nomograms were constructed based on the optimal combined models. Chronic hypertension was an independent risk factor for both EOPE and LOPE, while elevated placental perfusion parameters exerted a protetive effect. The combined model achieved optimal predictive performance, with AUCs of 0.980 (95% CI 0.968-0.992) for EOPE and 0.827 (95% CI 0.765-0.889) for LOPE. Internal bootstrap validation confirmed acceptable calibration, and DCA demonstrated positive net clinical benefit. Static nomograms established based on the optimal models enable individualized risk assessment for EOPE and LOPE. We developed and internally validated trimester-specific and combined prediction models to assess the risks of EOPE and LOPE, and constructed static nomograms based on the optimal models. The models achieved favorable apparent performance in this single-center cohort. Nevertheless, their generalizability remains unclear. External validation using independent cohorts is required before large-scale application in routine antenatal screening.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114495","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":"Comparative Therapeutic Effects of Cytokine-Rich Serum and Platelet-Rich Plasma in a Rat Model of Ovarian Ischemia-Reperfusion Injury.","authors":"Erol Karakaş, Hanifi Erol, Mustafa Ermiş, Gökhan Akçakavak, Nevzat Emre Aslan, Özhan Karataş","doi":"10.1007/s43032-026-02223-3","DOIUrl":"https://doi.org/10.1007/s43032-026-02223-3","url":null,"abstract":"<p><p>To evaluate and compare the protective effects of cytokine-rich serum (ACRS) and platelet-rich plasma (PRP) against ovarian ischemia-reperfusion (I/R) injury in a rat model of ovarian torsion and detorsion. Forty-two female Wistar albino rats were randomly allocated into control, PRP, ACRS, I/R, I/R + PRP, I/R+ACRS, and donor groups. Ovarian torsion was induced for two hours followed by detorsion. PRP or ACRS was administered following detorsion. Ovarian tissues were evaluated using histopathological assessment, follicle counting, and immunohistochemical analysis of anti-Müllerian hormone (AMH), cleaved Caspase-3, VEGFA, and α-SMA. Ischemia-reperfusion injury resulted in marked ovarian damage, characterized by increased follicular degeneration, congestion, hemorrhage, edema, stromal connective tissue changes, inflammatory cell infiltration, and elevated apoptotic activity. Both PRP and ACRS attenuated histopathological injury and apoptotic activity while improving follicular preservation. Compared with PRP, ACRS was associated with better preservation of primordial and tertiary follicles, fewer atretic follicles, higher AMH immunoreactivity, lower cleaved Caspase-3 immunoreactivity, and increased VEGFA immunoreactivity. No significant differences were observed in α-SMA immunoreactivity among groups. Both PRP and ACRS exert protective effects against ovarian I/R injury; however, ACRS was associated with more pronounced histological and molecular benefits. These findings suggest that ACRS may represent a promising biological approach in ischemic ovarian pathologies.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113740","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 Building and Application of a Machine Learning Model on Predicting Euploid Blastocysts in IVF Treatments Without PGT-A.","authors":"Zhenya Yuan, Jun Shao, Ya Wen, Mu Yuan, Mingzhu Bai, Xuemei Song, Xiaojie Huang","doi":"10.1007/s43032-026-02230-4","DOIUrl":"https://doi.org/10.1007/s43032-026-02230-4","url":null,"abstract":"<p><p>Embryologists could not know whether blastocysts were euploid or not in in-vitro fertilization treatments without preimplantation genetic testing for aneuploidy. However, preimplantation genetic testing for aneuploidy technology which might impair the developmental potency of blastocysts was in strict limitation in China. Therefore, a non-invasive method was necessary for embryologists to select euploid embryos as far as possible. A machine learning model based on preimplantation genetic testing for aneuploidy results, development dynamics, morphology of blastocysts and female age was built by two-logistic regression analysis. The area under the receiver operating characteristic curve of the model was 0.877. The accuracy rate, precision rate, recall rate, f-score, true negative rate, false positive rate, false negative rate of the model when performed in independent data set were 77.35%, 77.49%, 72.55%, 74.94%, 81.55%, 18.45%, 27.45%, respectively. Besides, the false positive rate of the model on predicting euploid blastocysts was significantly lower than Gardner grade and KIDScore D5. When selected blastocysts by the model, the frozen embryo transfer outcomes improved significantly than the frozen embryo transfer outcomes which selected blastocysts by Gardner selection. The predictive model had potency in selecting euploid blastocysts in in-vitro fertilization treatments without preimplantation genetic testing for aneuploidy technology.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114124","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":"An Ex Vivo Model for the Onset of Human Labor.","authors":"Marina Paul, Anna Paredes Barreda, Amy Gregson, Madeline King, Md Reduanul Hossain, Waleed M Hussein, Frederick R Walker, Roger Smith, Tamas Zakar, Jonathan W Paul","doi":"10.1007/s43032-026-02214-4","DOIUrl":"10.1007/s43032-026-02214-4","url":null,"abstract":"<p><p>During gestation, the myometrium remains relaxed but undergoes a phenotypic transformation near term that initiates labor. This coincides with increased expression of contraction-associated proteins (CAPs) and decreased expression of relaxation-associated proteins (RAPs), thereby promoting the development of powerful synchronous contractions that deliver the fetus. We do not yet fully understand the biochemical signaling pathways and physiological changes that occur as human myometrium transitions from a non-laboring to a laboring phenotype. An ex vivo model for the onset of human labor can expand our knowledge. This study aimed to assess whether non-laboring pregnant human myometrium in culture undergoes a phenotypic transformation that is consistent with transitioning toward a labor-like phenotype. Term, non-laboring pregnant human myometrium biopsies were collected. A small portion was immediately snap-frozen (0 h time point), while the remaining tissue was dissected into small pieces, incubated for 48 h in serum-free medium, and then snap-frozen. Changes in the mRNA abundance of key myometrial genes were assessed by qRT-PCR, and protein levels were quantified by Western blotting. Data were analyzed using GraphPad Prism. Myometrial expression of key CAPs, including GJA1, ESR1, PTGS2, NFκB1, NFκB3, IL1β, IL6, and AKR1C1, increased significantly, while expression of the RAPs, PLCL1, HSPB1, and HSPB6, was decreased significantly after 48 h of ex vivo culture. Term, non-laboring pregnant human myometrial explants undergo coordinated molecular remodeling during 48 h of ex vivo culture, with many changes paralleling those reported at term labor in vivo. These findings support prolonged explant culture as a model of the molecular transition toward a labor-like state, while also demonstrating that cultured non-laboring explants may no longer faithfully represent the original non-laboring phenotype.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2109-2132"},"PeriodicalIF":2.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13645985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149031405","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":"Maternal Metabolic Dysfunction and Uteroplacental Adaptation in Polyendocrine Metabolic Ovarian Syndrome Pregnancy.","authors":"Mina Amiri, Mahnaz Akbari Kamrani, Kowsar Qaderi, Mahsa Mohammad Ammoli","doi":"10.1007/s43032-026-02226-0","DOIUrl":"https://doi.org/10.1007/s43032-026-02226-0","url":null,"abstract":"<p><p>Polyendocrine metabolic ovarian syndrome (PMOS), formerly known as polycystic ovary syndrome (PCOS), is a multisystem endocrine-metabolic disorder that significantly increases the risk of adverse pregnancy outcomes, partly independently of obesity. PMOS patients frequently exhibit a characteristic metabolic-endocrine milieu of insulin resistance, hyperandrogenemia, dyslipidemia, and chronic low-grade inflammation. The physiological insulin resistance of pregnancy, driven by placental hormones, exacerbates these pre-existing disturbances and disrupts endometrial receptivity and placental function. These insults converge on conserved signaling pathways, phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT)/ mechanistic target of rapamycin (mTOR), nuclear factor kappa B (NF-κB)/ c-Jun N-terminal kinase (JNK), androgen receptor-mediated mitochondrial dysfunction and ferroptosis, and peroxisome proliferator-activated receptor (PPAR)-regulated lipid dysregulation, and impair trophoblast invasion, spiral artery remodeling, angiogenic balance, and nutrient transport. The resulting mitochondrial oxidative stress and lipotoxic injury contribute to early pregnancy loss, gestational diabetes, hypertensive disorders, preterm birth, and aberrant fetal growth. Concurrently, the dysmetabolic intrauterine environment programs offspring metabolic and reproductive dysfunction through epigenetic and developmental mechanisms. This review synthesizes current evidence linking the maternal metabolic milieu of PMOS to endometrial defects, placental structural and functional alterations, and long-term offspring outcomes. Emerging data on adipose-derived lipid mediators, fatty acid transporters, and inflammatory-metabolic crosstalk at the maternal-uteroplacental interface are examined. Therapeutic strategies such as lifestyle modification, metformin, and bariatric surgery in obese patients are appraised. Although some benefits have been reported, evidence across pregnancy outcomes remains inconsistent, and rigorous preconception trials are needed to establish efficacy. Elucidating how maternal metabolic signals contribute to placental injury and rigorously testing preconception interventions will be essential to refine risk stratification, develop targeted therapies, and interrupt the cycle of metabolic disease transmission in PMOS.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113856","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}