Biology of Reproduction最新文献

{"title":"Spatiotemporal dynamics of natural killer cell immune checkpoints Tim-3 and Lag-3 in human pregnancy: an integrated peripheral and decidual compartment analysis.","authors":"Daojing Li, Xianhong Tong, Yanyan Yang, Fangting Lu, Zuojun Shen, Yajing Liu, Yanshi Wang","doi":"10.1093/biolre/ioag126","DOIUrl":"10.1093/biolre/ioag126","url":null,"abstract":"<p><p>Pregnancy represents a unique state of immune adaptation requiring precise regulation to maintain tolerance toward the semi-allogeneic fetus. Although natural killer (NK) cells and T cells play central roles in maternal-fetal immunity, gestational stage-specific expression patterns of immune checkpoint molecules Tim-3 and Lag-3, especially regarding their soluble forms, remain poorly characterized. This study comprehensively investigates T-cell immunoglobulin and mucin domain-3 (Tim-3) and Lymphocyte-activation gene 3 (Lag-3) in maternal immune regulation by integrating peripheral blood and decidual tissue analyses. In decidual NK (dNK) cells, single-cell RNA sequencing identified four distinct subsets (dNK1, dNK2, dNK3, and proliferating NKp cells) and revealed subset-specific immune checkpoint profiles: Tim-3 was highly expressed in dNK1 and dNK2, whereas Lag-3 showed consistently low expression. Patients with recurrent pregnancy loss (RPL) exhibited significantly reduced Tim-3 expression in key dNK subsets. Gene set enrichment analysis (GSEA) of Tim-3+ dNK cells identified significant enrichment in immune-related pathways, including chemokine signaling, cytokine-cytokine receptor interaction, and apoptosis. Peripheral analyses revealed dynamic gestational changes: Tim-3+ NK cells peaked early and declined, while Tim-3+ T cells gradually increased. Soluble Tim-3 levels negatively correlated with membrane-bound Tim-3 on NK cells, suggesting shedding-mediated regulation. Collectively, these findings underscore the spatial and temporal specificity of immune checkpoint regulation during pregnancy and indicate that dysregulated Tim-3 expression in both decidual and peripheral NK cells may contribute to impaired maternal-fetal immune tolerance in RPL.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"789-801"},"PeriodicalIF":3.2,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148293242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compartment-specific aberrant YAP activation impairs endometrial receptivity and decidualization in recurrent implantation failure and recurrent pregnancy loss†.","authors":"Ziyao Yang, Lijie Feng, Wanting Fu, Xiao Han, Fan Yu, Beibei Bi, Wei Dai, Jing Sun, Ruizhe Zhang, Nuo Xu, Tianxiao Chen, Tianhua Tang, Linli Hu","doi":"10.1093/biolre/ioag145","DOIUrl":"10.1093/biolre/ioag145","url":null,"abstract":"<p><p>The Hippo-YAP signaling pathway is crucial for tissue homeostasis, yet its specific contribution to recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL) remains poorly understood. This study investigated Hippo-YAP signaling in physiological and pathological human endometrium, and its functional impact on endometrial receptivity and decidualization. We analyzed endometrial tissues from fertile controls, RIF patients, and RPL patients, complemented by mechanistic studies in Ishikawa cells and telomerase-immortalized human endometrial stromal cells. In fertile controls, YAP was progressively downregulated and phosphorylated from the proliferative to the secretory and decidual phases. Conversely, RIF and RPL endometria exhibited sustained YAP activation with distinct compartment-specific patterns: YAP was upregulated in the RIF epithelium, but in the RPL stroma. Mechanistically, estradiol promoted YAP nuclear translocation and activation via estrogen receptor, whereas progesterone antagonized this effect predominantly via progesterone receptor. Public ChIP-seq data analysis supported ERα/PR occupancy at the YAP promoter-proximal regulatory region. In functional assays, YAP overexpression significantly impaired JAR spheroid attachment to endometrial epithelial cells and suppressed key genes involved in receptivity. For stromal cells, YAP overexpression disrupted in vitro decidualization, as evidenced by morphological abnormalities and the suppression of PRL and IGFBP1. Conversely, inhibition of YAP using siRNA or verteporfin promoted epithelial receptivity and stromal decidualization. Our findings reveal that progesterone-mediated downregulation of YAP is a fundamental prerequisite for endometrial receptivity and decidualization. The spatiotemporal persistence of YAP activity, dictated by impaired progesterone signaling, orchestrates compartment-specific dysfunctions that underpin the clinical divergence between RIF and RPL.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"762-776"},"PeriodicalIF":3.2,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seminal ubiquitin as an independent predictor of severe sperm damage and ICSI outcomes: evidence for a redox-proteostasis axis in male infertility†.","authors":"Oya Korkmaz, Seda Karabulut, Pelin Macit","doi":"10.1093/biolre/ioag112","DOIUrl":"10.1093/biolre/ioag112","url":null,"abstract":"<p><p>Oxidative stress plays a central role in male infertility by inducing lipid peroxidation, DNA damage, and activation of sperm quality control mechanisms. However, the integrated relationship between oxidative stress, genomic damage, cellular stress response, and ubiquitin-mediated sperm elimination remains unclear. This study evaluated seminal plasma levels of malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), clusterin, and ubiquitin across distinct infertility phenotypes and assessed their predictive value. A total of 132 men were stratified into four groups based on sperm morphology and DNA fragmentation index (DFI): fertile normozoospermic, isolated teratozoospermia, isolated high DFI, and combined structural-genomic impairment. Biomarker concentrations were determined using enzyme-linked immunosorbent assay. All biomarkers increased progressively across infertility phenotypes (P < 0.001). Ubiquitin showed the strongest correlation with DFI (r = 0.71, P < 0.001) and remained the only independent predictor in multivariate linear regression (β = 0.41, P = 0.002). It also independently predicted the severe combined phenotype in logistic regression (OR = 1.19, 95% CI: 1.07-1.33, P = 0.001), with high discriminative performance (AUC = 0.88). In intracytoplasmic sperm injection (ICSI) cycles, elevated seminal ubiquitin levels were independently associated with reduced clinical pregnancy rates (adjusted OR = 0.74, P = 0.001) and improved model discrimination beyond female age and DFI (AUC 0.78-0.86). These findings support a redox-genomic damage-proteostasis axis in male infertility and identify ubiquitin as an integrative biomarker of severe sperm damage with clinical relevance beyond conventional semen analysis.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"802-812"},"PeriodicalIF":3.2,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148026693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disturbances of the placenta-brain axis in germ-free pregnant mice†.","authors":"Rosalind T B Herrington, Zhen Lyu, Ragavi Raman, Sarah E Seda, Claire Snyder, Nathan J Bivens, Zhentian Lei, Tanhaul Islam, Lloyd W Sumner, Trupti Joshi, Cheryl S Rosenfeld","doi":"10.1093/biolre/ioag103","DOIUrl":"10.1093/biolre/ioag103","url":null,"abstract":"<p><p>Maternal gut microbiota changes can profoundly shape on offspring health. The placenta may be vulnerable to maternal gut microbiota alterations. Placental disruptions can influence fetal brain development and underly risks for neurobehavioral disorders. Maternal gut microbiota disruptions might affect the placenta through alterations in bacterial short chain fatty acids. The hypothesis tested is that depletion of maternal gut microbiota, as may occur in pregnant women treated with antibiotics and germ-free mice, impacts bacterial short chain fatty acids in her fecal samples and in placenta and fetal brain in her conceptuses. We assessed whether transcriptomic changes would be evident in placenta and fetal brain from conceptuses derived from germ-free relative to multi-pathogen free pregnant females. Maternal germ-free status reduced the concentrations of all measured short chain fatty acids within the stool. Two-methylbutanoic acid was significantly increased in male and female placenta and fetal brain samples in conceptuses from germ-free dams. In female and male placenta, several Prl form had altered expression in conceptuses from germ-free dams. In male placenta from germ-free dams, Hsd11b2 showed increased expression. Decreased expression of Sl6a2 in female fetal brain from germ-free dams might influence uptake of catecholamines. Results reveal depletion of maternal microbiota can lead to striking effects on the placenta-fetal brain axis. Findings raise concern as to whether maternal microbiota alterations due to other intrinsic or extrinsic factors, namely antibiotic treatment, might impact placental and neural transcriptomic profiles. Underlying mechanisms remain uncertain but may relate to changes bacterial metabolites transferred from mother to conceptus.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"890-910"},"PeriodicalIF":3.2,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147939979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bardoxolone methyl modulates Nrf2/NF-𝜅B signaling in turkey uterovaginal junction organoids with potential use for improving reproductive longevity in breeder hens.","authors":"Pitchaya Coleman, Sunantha Kosonsiriluk, David R Brown, Scott O'Grady, Marissa M Studniski, Ben W Wileman, Kahina S Boukherroub","doi":"10.1093/biolre/ioag122","DOIUrl":"10.1093/biolre/ioag122","url":null,"abstract":"<p><p>Turkey production faces significant challenges in maintaining breeder flock fertility, due in part to increased inflammation and accelerated reproductive aging in the distal reproductive tract. These conditions are associated with chronic oxidative stress and compromised cellular function. Activation of the antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2), and inhibition of the pro-inflammatory nuclear factor kappa B (NF-κB) may ameliorate these conditions. This approach remains unexplored in avian reproductive tissues, which possess distinct metabolic and physiological profiles from mammals. This study was designed to investigate the effects of Nrf2/NF-κB modulation in turkey reproductive cells using the Nrf2 activator, bardoxolone methyl (BM), in vitro and further evaluate the effects of this antioxidant in vivo. Turkey uterovaginal junction (UVJ) organoids were treated with BM and exposed to oxidant hydrogen peroxide. Treatment with 0.5 μM BM increased viability, reduced reactive oxygen species production, and inhibited nuclear translocation of NF-𝜅B. Furthermore, BM promoted Nrf2 nuclear accumulation and upregulated antioxidant markers, including heme oxygenase 1 and thioredoxin reductase 1. Short-term treatment with BM in breeder hens did not adversely affect body weight, egg production, or reproductive immune cell localization. Transcriptomic analysis of vaginal tissues revealed downregulation of oxidative phosphorylation and inflammatory markers, including secreted phosphoprotein 1. In the UVJ, reduced redox-sensitive transcripts suggested lowered baseline physiological stress. Direct exposure of turkey spermatozoa to BM did not impair viability, morphology, or motility. These findings suggest that targeting the turkey antioxidant response via the Nrf2/NF-κB axis may serve as a safe potential strategy for enhancing reproductive longevity.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"724-738"},"PeriodicalIF":3.2,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148222487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential expression of microRNAs after induction of endometriosis in baboons†.","authors":"Ramanaiah Mamillapalli, Hanna Surmann, Niraj Joshi, Gregory Burns, Fazleabas T Asgerally, Hugh S Taylor","doi":"10.1093/biolre/ioag140","DOIUrl":"10.1093/biolre/ioag140","url":null,"abstract":"<p><p>Endometriosis is an inflammatory chronic gynecological condition that affects 10-15% of reproductive-age women which causes pelvic pain and infertility. The disease is characterized by the growth of endometrial tissue outside the uterine cavity. Currently, early diagnosis of endometriosis is difficult due to non-specific symptoms and the absence of reliable biomarkers. Understanding these early molecular alterations could support the development of diagnostic tools for timely detection and treatment. The objective of this study was to identify changes in circulating microRNA (miRNA) profiles during the initial stages of endometriosis using a longitudinal non-human primate baboon model. Endometriosis was induced in female baboons by laparoscopic inoculation of menstrual endometrial tissue and plasma was collected at various timepoints. Plasma miRNAs at 3, 6, 9, and 15 months were analyzed using RNA sequencing. A total of 2731 miRNAs were detected, 76 of which showed significant differences at least at one time point. There are four, three, and one miRNA exclusively differentially expressed at 3-, 6- and 9-month timepoints, respectively, and 68 miRNAs at 15 months. Four miRNAs (miR-210-3p, miR-448, miR-1260a/1260b, and miR-1298-5p) exhibited significant alterations across all time points. Of these, miR-210-3p increased, while the others decreased significantly. Hierarchical clustering revealed separation between the early (pre-inoculation and 3 months) and late (3 and 15 months) stages, indicating progressive divergence of miRNA profiles. These findings identify candidate miRNAs that may provide insight into early pathophysiological mechanisms and represent candidate circulating biomarkers associated with temporal molecular changes following disease induction, warranting further validation.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"739-749"},"PeriodicalIF":3.2,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new constitutive Foxl2-Cre mouse model reveals Foxl2-derived cell fate in reproductive and non-reproductive tissues†.","authors":"Barbara Nicol, Artiom Gruzdev, Ciro Amato, Chang Liu, Gregory J Scott, Thomas B Hagler, Manas K Ray, Humphrey Hung-Chang Yao","doi":"10.1093/biolre/ioag116","DOIUrl":"10.1093/biolre/ioag116","url":null,"abstract":"<p><p>FOXL2 is a highly conserved transcription factor that is essential for ovarian development and female fertility. In humans, FOXL2 mutations or deletions cause blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) leading to eyelid defects and, in BPES type I, primary ovarian insufficiency. BPES is also associated with a wide range of less common phenotypes such as craniofacial features, cleft palate, or heart defects. In this study, we generated a new constitutive Foxl2-Cre mouse model using CRISPR/Cas9 editing. Crossing Foxl2-Cre mice with Rosa-tdTomato reporter confirmed robust and specific labeling of FOXL2+ cells during fetal development. We provide a detailed characterization of the permanent labeling of cells that, at any time in development, expressed Foxl2, with a particular interest on organs associated with a spectrum of features identified in BPES patients. Our model effectively targeted key reproductive tissues, such as fetal ovarian somatic cells, including granulosa, interstitium and theca-cell precursors, the anterior pituitary, and mesenchymal cells of the uterus and oviduct. We also identified Foxl2-derived cells in the supporting-like cells of the testis, as well as in the peri-urethral cells of the external genitalia. Beyond the reproductive organs, Foxl2-derived cells were identified in several other tissues relevant to BPES, including the head, palate, and the outflow tract of the heart. Overall, this Foxl2-Cre model provides a new tool for reproductive organ studies, and our characterization of Foxl2-derived cell fate brings a new perspective into the potential roles of FOXL2 in the wide spectrum of clinical features associated with BPES.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"832-849"},"PeriodicalIF":3.2,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal e-cigarette exposure reprograms the cardiac proteome and increases ischemia susceptibility in a sex-dependent manner†.","authors":"Jiazichao Tu, Jie Jian, Yong Li, Jacob Chavez, Quanqing Zhang, Rongjun Yu, Wansu Yu, Lubo Zhang, Daliao Xiao","doi":"10.1093/biolre/ioag128","DOIUrl":"10.1093/biolre/ioag128","url":null,"abstract":"<p><p>Prenatal electronic cigarette exposure has been associated with adverse cardiovascular outcomes in offspring, yet the underlying molecular mechanisms remain poorly understood. Using a rat model of gestational electronic cigarette aerosol exposure combined with quantitative liquid chromatography-tandem mass spectrometry proteomics and integrated Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, protein-protein interaction, and Evolutionary Genealogy of Genes: Non-Supervised Orthologous Groups analyses, we identified profound and sexually dimorphic alterations in the neonatal cardiac proteome. There was extensive mitochondrial and metabolic dysregulation in the developing heart following prenatal electronic cigarette exposure. In male offspring, enriched pathways included oxidative phosphorylation, tricarboxylic acid cycle activity, and respiratory chain assembly, indicating disruption of mitochondrial energy metabolism. In contrast, female offspring exhibited prominent dysregulation of mitochondrial chaperones (Hspa9 and Hspa4) and ribosomal proteins (Rps11, Rpl11, and Rps3), suggesting impaired proteostasis and translational capacity. Protein-protein interaction and Kyoto Encyclopedia of Genes and Genomes analyses further revealed sex-dependent perturbations of signaling and structural protein networks critical for cardiac contractility, cardiomyopathy progression, and myocardial stress resilience. Males primarily showed alterations in sarcomeric, structural, and metabolic proteins, whereas females exhibited widespread disruption of G protein-coupled receptor/cyclic adenosine monophosphate/protein kinase A (cAMP/PKA)-mediated regulatory pathways. These early-life proteomic alterations translated into functional deficits in adulthood, with males displaying impaired baseline cardiac function and exacerbated ischemia/reperfusion injury, while females showed preserved baseline function but heightened susceptibility to ischemia/reperfusion stress. Collectively, these findings demonstrate that prenatal electronic cigarette exposure programs long-lasting, sex-specific cardiac vulnerability through early-life proteomic reorganization, providing mechanistic insight into developmental cardiotoxicity and informing risk assessment during pregnancy.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"923-938"},"PeriodicalIF":3.2,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Downregulation of CLU mediates CART-induced apoptosis and suppressed proliferation in bovine granulosa cells†.","authors":"Junli Cheng, Meng Liu, Yuting Qiao, Zhiwei Zhu, Guangwen Zhang, Pengfei Li","doi":"10.1093/biolre/ioag124","DOIUrl":"10.1093/biolre/ioag124","url":null,"abstract":"<p><p>This study aimed to elucidate the molecular mechanisms by which cocaine- and amphetamine-regulated transcript peptide (CART) regulates granulosa cell (GC) fate in Bos taurus follicles. Bovine GCs were used as an in vitro model, and tandem mass tag-based quantitative proteomics was performed to identify differentially expressed proteins (DEPs) following CART treatment. CART significantly downregulated clusterin (CLU), the most altered DEP (P < 0.05). Functional studies demonstrated that CLU knockdown, mimicking CART action, significantly promoted GC apoptosis, as evidenced by increased Annexin V and PI fluorescence signals (all P < 0.05). CLU knockdown also significantly suppressed proliferation, with cell viability reduced by approximately 19-20% compared to controls in the CCK-8 assay (P < 0.05). CLU knockdown decreased the anti-apoptotic protein B-cell lymphoma-extra large (Bcl-XL, P < 0.05) and cell-cycle regulators cyclin D2 (CCND2, P < 0.05), cyclin-dependent kinase 1 (CDK1, P < 0.05), and proliferating cell nuclear antigen (PCNA, P < 0.05), while elevating pro-apoptotic effectors BCL2-associated X (BAX, P < 0.05) and cleaved caspase-3 (CASP3, P < 0.05). However, CART co-treatment did not further exacerbate these effects (P > 0.05), indicating that CLU is a key effector molecule mediating CART's pro-apoptotic action. CART's pro-apoptotic and anti-proliferative effects on GCs likely also involve other downstream targets in the altered proteome. These results demonstrate that CART reprograms the GC proteome and that downregulation of CLU is a pivotal event driving this shift toward a pro-apoptotic and anti-proliferative state, providing insights into the protein-centric mechanisms by which CART influences GC fate.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"850-865"},"PeriodicalIF":3.2,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced circulating polyamines in polyendocrine metabolic ovarian syndrome patients and the impact of putrescine on ovarian function and fertility in a murine PMOS model†.","authors":"Subrata Das, Joseph R D Fernandes, P T Nikhil, S Narayana, Gayatri Shinde, Srabani Mukherjee, Chandrika Anand, N Suchetha Kumari, Sridev Mohapatra, Arnab Banerjee","doi":"10.1093/biolre/ioag139","DOIUrl":"10.1093/biolre/ioag139","url":null,"abstract":"<p><p>GnRH is essential for regulating the reproductive system in mammals. Recent research has shown that polyamines, biogenic amines produced in body, can regulate gonadotropin-releasing hormone (GnRH) levels. These polyamine levels are affected by metabolic disorders like diabetes and obesity. However, it remains unclear whether changes in polyamine expression are related to polyendocrine metabolic ovarian syndrome (PMOS), which is characterized by altered GnRH patterns. Circulatory polyamine levels were measured in PMOS patients. In a study on prepubertal female Balb/c mice induced with a PMOS-like condition using DHEA, the mice were treated with polyamines (putrescine, agmatine, and DFMO) for 5 days. The effects on body weight, serum glucose, testosterone, GnRH, GnIH levels, and gene expression related to ovarian inflammation and folliculogenesis were observed. The study found that circulatory polyamines (putrescine, spermidine, and spermine) are lower in PMOS patients than in healthy individuals. A single dose of putrescine improved PMOS-like symptoms in mice by reducing GnRH, glucose, testosterone levels, body weight, and inflammation in the ovary. Exogenous polyamine treatment increased endogenous polyamine markers in the hypothalamus and ovary, thereby improving fertility and pregnancy outcomes in PMOS mice by regulating key uterine markers. These findings suggest that circulating polyamine levels vary between PMOS and healthy individuals. Exogenous polyamine treatment enhances GnRH metabolism in the hypothalamus by modulating endogenous polyamine genes, thereby improving PMOS traits and ovarian morphology, reducing serum testosterone levels, and supporting successful pregnancy. The authors thereby suggest that endogenous polyamines are key to the pathophysiology of PMOS, and that exogenous polyamines could be a potential target for PMOS management.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"813-831"},"PeriodicalIF":3.2,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148366820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}