Biology of Reproduction最新文献

{"title":"Follicle identification in primate ovaries via machine learning†.","authors":"James P Sluka, Riley Israels, Colette Lund, Parth Ravindra Rao, Param Nagda, Yian Ding, Alessia Daniele, Suzanne W Dietrich, Mary B Zelinski, Karen H Watanabe","doi":"10.1093/biolre/ioag149","DOIUrl":"10.1093/biolre/ioag149","url":null,"abstract":"<p><p>Studies of ovarian health and aging rely on estimates of the ovarian reserve, i.e., the number of healthy ovarian follicles. We present a machine learning pipeline to classify preantral ovarian follicles in histology images from non-human primates. Ovarian tissue from 11 monkeys were fixed, sectioned, stained, and imaged. A total of 7770 preantral follicles were manually annotated in 18 histology section images using a standardized protocol, with annotations reviewed by an expert. Using a transfer learning approach, we retrained a ResNet34 convolutional neural network to classify individual follicle images into six developmental stages. The model achieved high accuracy during training (>98%) and good performance on validation and test sets (75.3% and 72.4%, respectively), with most errors confined to adjacent stages, suggesting the network learned an implicit developmental ordering of follicles. All code, annotated datasets, and trained models are publicly available to support reuse and further exploration. Application of this model for determining follicle numbers will be useful in studies of primates, and perhaps humans. For example, it may be used for determining drug or environmental toxicant effects on follicle populations or for fertility preservation planning. Importantly, this model will facilitate the study of ovarian aging and follicle depletion in a translational animal model and for developing interventions to preserve ovarian reserve, extend fertility, and delay menopause in women.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1078-1090"},"PeriodicalIF":3.2,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468709","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":"Correction to: Injectable contraceptives differentially affect the hypothalamic-pituitary-gonadal axis and amenorrhea incidence.","authors":"","doi":"10.1093/biolre/ioag192","DOIUrl":"10.1093/biolre/ioag192","url":null,"abstract":"","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1354"},"PeriodicalIF":3.2,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900341","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":"OVOL2 reinforces epithelial identity and promotes SynT-I differentiation in the mouse placenta†.","authors":"Violet S Patterson, Mariyan J Jeyarajah, Amanda M Rampersaud, Gargi Jaju Bhattad, Stephen J Renaud","doi":"10.1093/biolre/ioag157","DOIUrl":"10.1093/biolre/ioag157","url":null,"abstract":"<p><p>The placenta establishes the maternal-fetal interface during pregnancy, enabling the selective exchange of nutrients and gases between maternal and fetal circulations. In humans and mice, this exchange surface is lined by multinucleated epithelial layers called the syncytiotrophoblast (SynT), which in the mouse placenta is organized into two distinct layers, SynT-I and SynT-II. SynT formation from trophoblast precursors requires epithelial plasticity to permit cell differentiation, fusion, and morphogenesis, while preserving epithelial integrity to maintain the maternal-fetal exchange barrier. However, the mechanisms that safeguard epithelial features during SynT development remain unclear. OVO-like 2 (OVOL2), a transcriptional repressor of mesenchymal-associated programs and key regulator of epithelial identity, is highly expressed in the mouse placenta and essential for its development. We hypothesized that OVOL2 promotes SynT lineage formation by restraining mesenchymal-associated transcriptional programs during trophoblast differentiation. To test this, placental development was examined following Ovol2+/- matings, and wild-type and Ovol2-deficient trophoblast stem (TS) cells were analyzed under stem conditions or differentiated with CHIR99021 to enrich for SynT lineages. SynT-I lineage development was disrupted in both Ovol2-deficient placentas and differentiating TS cells, whereas SynT-II-associated differentiation appeared less severely affected. Chromatin profiling identified OVOL2 binding near genes associated with epithelial-to-mesenchymal transition, including Id1, Zeb1, and Vim, which were upregulated in Ovol2-deficient trophoblasts. Consistent with these observations, Ovol2-deficient cells showed elevated levels of mesenchymal markers such as ZEB1 and Vimentin and reduced levels of epithelial markers including E-cadherin. These findings identify OVOL2 as a critical regulator of SynT-I lineage formation and epithelial identity in the mouse placenta.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1239-1254"},"PeriodicalIF":3.2,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576942","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":"Meiosis and Ageing in Mammals.","authors":"Ian R Adams","doi":"10.1093/biolre/ioag230","DOIUrl":"https://doi.org/10.1093/biolre/ioag230","url":null,"abstract":"<p><p>Meiosis is a specialized form of cell division that plays an essential role in mammalian sexual reproduction to reduce the ploidy of the developing germ cells so that each gamete transmits one copy of each chromosome to the next generation. In humans, approximately 20% of conceptions inherit the wrong number of chromosomes, with the vast majority of these aneuploid embryos arising from de novo chromosome segregation errors during meiosis. These inherited autosomal aneuploidies usually arise maternally during oocyte meiosis, and are strongly affected by maternal age. Paternally-inherited autosomal aneuploidies occur less frequently, and are also affected by age. Depending on the specific chromosome involved, aneuploid human embryos typically die before implantation, are miscarried, or develop genetic disorders such as Down syndrome. Despite the significant impact of inherited aneuploidies on the incidence of human genetic disease and reproductive outcomes, the molecular mechanisms through which ageing impacts on the fidelity of meiotic chromosome segregation in mammals remain poorly understood. This review will outline some of the effects that ageing is thought to have on meiotic mammalian chromosomes to perturb meiotic chromosome segregation and impact on the incidence of inherited aneuploidies.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178806","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":"In Vitro Fertilization in the Age of In Vitro Gametogenesis.","authors":"I Glenn Cohen, Eli Y Adashi","doi":"10.1093/biolre/ioag223","DOIUrl":"https://doi.org/10.1093/biolre/ioag223","url":null,"abstract":"","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178360","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":"Functional and mechanistic characterization of bone morphogenetic protein 15 (BMP15) in regulating ovarian development in Japanese eel (Anguilla japonica)†.","authors":"Yuting Ci, Chenpeng Zuo, Xiao Jing, Ziyi Zhao, Xuanhan Zhang, Yun Li, Xin Qi","doi":"10.1093/biolre/ioag210","DOIUrl":"https://doi.org/10.1093/biolre/ioag210","url":null,"abstract":"<p><p>The Japanese eel (Anguilla japonica) is a commercially important species whose captive reproduction remains challenging. Bone morphogenetic protein 15 (BMP15) is an oocyte-derived factor that plays a key role in regulating folliculogenesis; however, its function in Japanese eel is unclear. In this study, the full-length Japanese eel bmp15 cDNA was cloned and bioactive recombinant BMP15 protein was produced. Weekly co-administration of recombinant BMP15 with FSH and LHRHa for 10 weeks significantly promoted ovarian development, as indicated by increased gonadosomatic index (GSI), larger oocyte area, and elevated serum vitellogenin (VTG) levels compared to hormone treatment alone. Integrated multi-omics analyses suggested that BMP15 exerts its biological functions through a coordinated regulatory network involving anabolic metabolism, glycerophospholipid biosynthesis, nutrient transport, extracellular matrix remodeling, and suppression of steroidogenesis. These findings are consistent with a mechanistic model in which BMP15 simultaneously promotes growth, maintains follicular homeostasis, and optimizes oocyte quality by controlling maturation timing. Our findings identify BMP15 as a potential key regulator of ovarian development in Japanese eel and highlight its potential as a novel homologous factor for improving artificial maturation strategies in eel aquaculture.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164764","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":"Understanding Stallion Sperm Capacitation: Species-Specific Mechanisms, Cryocapacitation, and Implications for IVF.","authors":"Artur M Freitas-Martins, Marion Papas, Barend M Gadella, Anthony N J Claes, Tom A E Stout, Bart Leemans","doi":"10.1093/biolre/ioag229","DOIUrl":"https://doi.org/10.1093/biolre/ioag229","url":null,"abstract":"<p><p>Until recently, no repeatable protocol for equine in vitro fertilization (IVF) had been established, despite decades of trying. Recent studies have demonstrated reproducible IVF outcomes under specific experimental conditions, bringing equine IVF into a new perspective. Prolonged incubation of stallion spermatozoa in a TALP based medium supplemented with penicillamine, hypotaurine and epinephrine (PHE) appears to be important factors of protocols that support sperm capacitation and markedly improved IVF outcomes. The sperm capacitation procedure has now been applied successfully using both fresh and frozen-thawed stallion semen, with the latter requiring a shorter pre-incubation period. Here, we review the molecular, structural, and metabolic processes that drive capacitation in stallion spermatozoa, with comparisons to better-characterized mechanisms in other mammals, focusing on changes in sperm membrane composition, energy metabolism, cytoplasmic content, and on the influences of seminal plasma and the female reproductive tract. Because the newly developed IVF protocol appears to be shorter with frozen-thawed semen, special attention is given to capacitation-like changes triggered by cryopreservation, and their consequences for sperm function and fertilizing capacity. Importantly, although successful fertilization can be achieved under these conditions, this does not constitute direct evidence that the molecular mechanisms governing stallion sperm capacitation have been fully elucidated. Rather, these protocols provide a robust experimental platform for investigating these mechanisms in the horse.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164415","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":"Expression and role of SIRT1 and SIRT6 in porcine conceptus and trophoblasts: relevance to early placenta development†.","authors":"Magdalena Szymanska, Agnieszka Blitek","doi":"10.1093/biolre/ioag227","DOIUrl":"https://doi.org/10.1093/biolre/ioag227","url":null,"abstract":"<p><p>Placenta insufficiency, arising from impaired trophoblast (Tr) function, contributes to early embryo loss and fetal growth restriction. Sirtuin (SIRT) 1 and SIRT6 are redox modulators in early embryonic development, yet their roles in porcine Tr remain unclear. This study examined the expression and roles of SIRT1/6 in porcine Tr during early pregnancy. Conceptus and Tr tissues from days 12 to 30 pregnant gilts were analyzed for SIRT1/6 expression. Then, day-15 Tr cells were treated with SIRT1/6 modulators to assess gene expression, cell viability, cell-cycle proteins, cell adhesion, cytokine synthesis, and reactive oxygen species (ROS) generation under control and hydrogen peroxide (H2O2)-induced oxidative stress. SIRT1 mRNA expression increased with placenta development (days 15-30 of gestation), while its protein levels remained unchanged. SIRT6 protein abundance was greater during implantation (day-15 conceptuses) and at placentation onset (day-20 Tr) compared with day-30 Tr. SIRT1 activation stimulated mRNA expression of mitochondrial biogenesis regulators (NFE2L2, TFAM) and respiratory chain components (MT-ND1-2, MT-ATP6/8). The SIRT6 activator induced NRF1, TFAM, and all 13 mitochondrial respiratory subunit genes (MT-ND1-6, MT-CYB, MT-CO1-3, MT-ATP6/8). Both activators stimulated cell proliferation, possibly by shortening mitosis as evidenced by reduced phospho-H3-S10 levels. IL6 synthesis was upregulated, while IFNγ production was decreased in these cells. SIRT6 activation counteracted H2O2-induced oxidative stress, reducing ROS and supporting cell viability, while amplifying stress-induced mitochondrial pathways. In conclusion, SIRT1/6 may support porcine Tr development and function. SIRT6 appears to modulate the response of peri-implantation conceptuses to oxidative stress, suggesting its potential as a target for improving prenatal survival.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164053","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":"Glucocorticoid exposure disrupts vascular-immune interactions and impairs steroidogenesis in the fetal mouse testis†.","authors":"Satoko Matsuyama, Lauren Hudepohl, Kazuhiro Matsuyama, Shu-Yun Li, Meghana Ginugu, Xiaowei Gu, Matthew J Kofron, Vikram Ravindra, Tetsuo Shoda, Tony DeFalco","doi":"10.1093/biolre/ioag228","DOIUrl":"10.1093/biolre/ioag228","url":null,"abstract":"<p><p>Antenatal corticosteroid (ACS) therapy, typically using dexamethasone (Dex), is a cornerstone of improving preterm infant survival by accelerating lung maturation. However, its systemic effects on other developing organs remain poorly understood. Here, we reveal a previously unrecognized impact of prenatal Dex exposure on fetal testis development, with implications for male reproductive health. Analysis of fetal testes from a Dex-based ACS mouse model revealed that Dex suppressed androgen synthesis by reducing Leydig cell number and downregulating steroidogenic pathways. Dex also activated immune programs, induced CD163+ M2c macrophages and IL-10 signaling, and promoted endothelial expansion. In response to aberrant pro-angiogenic signals, vascular architecture was disrupted: capillary density and pericyte gene expression declined, while blood vessel diameter increased. Transcriptomic analyses revealed downregulation of androgen response and cholesterol metabolism pathways, alongside upregulation of immune and coagulation signatures. Analyses of fetal ovaries revealed a sexually dimorphic and organ-specific effect of ACS treatment, in which ovarian gene expression during this window of development remained unaffected. Our findings uncover an immune-vascular mechanism linking prenatal Dex to impaired steroidogenesis, providing new insight into potentially broad effects of glucocorticoid exposure.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164075","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 Single-Cell Transcriptomic Map Reveals Platelet-Rich Plasma-Induced Endometrial Microenvironment Remodeling in Recurrent Implantation Failure.","authors":"Yue Jiang, Jingwen Jiang, Hui Zhang, Jingyu Liu, Jun Xing, Chenyang Huang, Yingchun Zhu, Fangfang He, Zhilong Wang, Guijun Yan, Ruiwei Jiang","doi":"10.1093/biolre/ioag224","DOIUrl":"https://doi.org/10.1093/biolre/ioag224","url":null,"abstract":"<p><p>Intrauterine infusion of platelet-rich plasma shows clinical promise as a regenerative therapy for patients with repeated implantation failure, yet the precise cellular and molecular mechanisms governing its in vivo effects on the human endometrium remain poorly understood. To elucidate these mechanisms at high resolution, we performed single-cell RNA sequencing on paired endometrial biopsies collected from patients during the proliferative phase, both before and shortly after intrauterine platelet-rich plasma infusion. Our analysis reveals that platelet-rich plasma acts as a potent modulator of the endometrial microenvironment by inducing extensive transcriptional reprogramming within resident cell populations. Alongside the direct stimulatory effects of PRP on various cell lineages, stromal cells emerged as key mediators contributing to this regenerative response, suppressing developmental plasticity pathways while concomitantly upregulating functions crucial for tissue regeneration, including cytoskeletal remodeling, pro-angiogenic signaling, and immune modulation. These reprogrammed stromal cells are predicted to serve as functional hubs, potentially driving enhanced paracrine networks that support robust angiogenesis through endothelial cell expansion and promote a growth-favorable epithelial phenotype via secreted growth factors. Notably, platelet-rich plasma infusion also induced a marked expansion and activation of specific tissue-resident natural killer cell subsets, indicating a recalibration of the local immune landscape. This study highlights that platelet-rich plasma orchestrates a multifaceted regenerative program where direct cellular stimulation converges with reprogrammed stromal-driven paracrine signaling to facilitate vascularization, epithelial growth, and immunological recalibration in the endometrium.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163989","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}