Fanny Morin, Camilla H K Hughes, Vickie Roussel, Nicholas Gevry, Bruce D Murphy
{"title":"Double knockout of steroidogenic factor 1 (NR5A1) and liver receptor homolog 1 (NR5A2) in the mouse ovary results in infertility due to disruption of follicle development and ovulation†.","authors":"Fanny Morin, Camilla H K Hughes, Vickie Roussel, Nicholas Gevry, Bruce D Murphy","doi":"10.1093/biolre/ioaf079","DOIUrl":"10.1093/biolre/ioaf079","url":null,"abstract":"<p><p>Liver receptor homolog 1 (LRH-1; Nr5a2) and steroidogenic factor 1 (SF-1; Nr5a1) are two closely related orphan nuclear receptors that bind to the same genomic motif. Conditional depletion of either of these receptors in the ovary results in infertility, but through different mechanisms, with SF-1 being critical early in ovarian development and LRH-1 regulating ovulation. We conditionally depleted both LRH-1 and SF-1 from the ovary, using two different models of conditional depletion, generating two lines of double conditional knockout (dko) mice. In one, we used the Amhr2Cre (Amhr2-dko) mouse, where depletion is initiated in the prenatal ovary before the stage of germ cell nest breakdown. In the other, we employed Cyp19a1Cre (Cyp19a1-dko)-mediated depletion, which is initiated following formation of the follicular antrum. Both models were completely anovulatory and infertile, and no ovulation occurred following administration of exogenous gonadotropins. The Amhr2-dko mouse had dramatically reduced follicular populations at every stage of development, as well as disrupted extracellular matrix, characterized by dysregulation of collagen and laminin expression in reproductively mature mice, reduced expression of steroidogenic genes, dysregulated lipid metabolism, and inhibited granulosa cell proliferation. The latter resulted in a phenotype of reduced ovarian size in this model. The Cyp19al dko mouse displayed dysregulation of luteinizing hormone (LH) response and ovulatory mechanisms and increased activation of the activin/inhibin signaling axis, suggesting impaired gonadotropin responsiveness. In summary, both dko models demonstrated a phenotype of complete infertility, confirming the critical importance of both LRH-1 and SF-1 in ovarian function.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"182-198"},"PeriodicalIF":3.1,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784555","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}
Paulina Lipinska, Katrien Smits, Ann Van Soom, Krishna Chaitanya Pavani, Ewelina Warzych
{"title":"Follicular-fluid extracellular vesicles support energy metabolism of bovine oocytes, improving blastocyst development and quality†.","authors":"Paulina Lipinska, Katrien Smits, Ann Van Soom, Krishna Chaitanya Pavani, Ewelina Warzych","doi":"10.1093/biolre/ioaf096","DOIUrl":"10.1093/biolre/ioaf096","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) from follicular fluid (FF) seem to play a significant role in communication within ovarian follicles in several species. The present study aimed to examine the supporting effect of FF-derived small EVs (FF-sEVs) during in vitro maturation (IVM) of bovine cumulus-oocyte complexes (COCs) under conditions of disturbed energy metabolism. Bovine COCs were matured in vitro with inhibitors targeting lipid metabolism (etomoxir) or glucose metabolism (iodoacetate combined with dehydroepiandrosterone), in the presence or absence of FF-sEVs. Following maturation, oocytes and cumulus cells were analyzed by real-time quantitative polymerase chain reaction (qPCR) and stained to visualize lipid droplets. The uptake of FF-sEVs was visualized by fluorescent labeling. In vitro fertilization and embryo culture were followed by mass spectrometry analysis of hatched blastocysts. We demonstrate for the first time that FF-sEVs are transported from the medium into the oocytes, via the cumulus cells and through transzonal projections into the perivitelline space and ooplasm. Cumulus cells under metabolic stress conditions exhibit an increased FF-sEV uptake from the maturation medium. FF-sEV supplementation during metabolic stress conditions enhances the MII rate in oocytes and positively affects subsequent embryo development and quality revealed by altered metabolic activity. Lipid droplet parameters and gene expression in cumulus cells and oocytes are affected by FF-sEV supplementation, which is more pronounced in cumulus cells. Our findings show that FF-sEV supplementation during IVM under metabolic stress conditions significantly affects COCs, with a positive effect on further blastocyst quality. We provide novel insights into the role of FF-sEVs in oocyte maturation and blastocyst development.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"109-126"},"PeriodicalIF":3.1,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969467","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}
Juan F Garcia Rivas, Wendy Duan, Bethan Wilson, Meghan Riddell
{"title":"A single cell transcriptomic resource of murine implantation sites at embryonic days 6.5 and 10.5.","authors":"Juan F Garcia Rivas, Wendy Duan, Bethan Wilson, Meghan Riddell","doi":"10.1093/biolre/ioaf155","DOIUrl":"https://doi.org/10.1093/biolre/ioaf155","url":null,"abstract":"","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607288","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":"Is NAD+ a key factor in ovarian aging and dysfunction? Insights and uncertainties from current research.","authors":"Valeria Cordone, Teresa Vergara, Stefano Falone, Carla Tatone, Giovanna Di Emidio","doi":"10.1093/biolre/ioaf140","DOIUrl":"https://doi.org/10.1093/biolre/ioaf140","url":null,"abstract":"<p><p>Recent findings highlight NAD+ as a central regulator of various cellular processes, including energy metabolism, stress response, and aging. The growing evidence of the benefits associated with dietary NAD+ precursors has elevated NAD+ to a promising therapeutic target for addressing female infertility. This review aims to evaluate existing literature on the mechanisms governing the availability and utilization of NAD+ in the ovaries and its alterations in female reproductive disorders, with a particular focus on ovarian aging and dysfunction including polycystic ovary syndrome (PCOS) and premature ovarian insufficiency (POI). Alongside data from in vivo and in vitro studies on various NAD+ boosters, this review incorporates findings from research on genetic mutations, polymorphisms in human and animal populations, and insights from transgenic animal models. The present work emphasizes that NAD+ deficiency is largely driven by a combination of factors, including heightened consumption, impaired utilization efficiency, and diminished biosynthesis or transport. Analysing these aspects, we suggest that the ovary possesses its own unique NAD+ metabolism, but our understanding of the mechanisms governing it is still in its infancy. Key questions remain unanswered, such as how NAD+ and its precursors are transported into oocytes and ovarian cells, their specific preferences for different NAD+ precursors, as well as the specific changes associated with different ovarian dysfunctions. Finally, in this review methods for studying NAD+ metabolism are reported as essential tools to properly investigate the potential of NAD+ boosting therapies for counteracting ovarian aging and dysfunction.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590379","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}
Elizabeth Varghese, Mary E Soliman, Hong Lou, Raghuveer Kavarthapu, Maria De La Luz Sierra, Jacqueline C Yano Maher, Veronica Gomez-Lobo
{"title":"A Comparative Analysis of Fixatives for Improved Histological Integrity in the Human Ovary.","authors":"Elizabeth Varghese, Mary E Soliman, Hong Lou, Raghuveer Kavarthapu, Maria De La Luz Sierra, Jacqueline C Yano Maher, Veronica Gomez-Lobo","doi":"10.1093/biolre/ioaf117","DOIUrl":"https://doi.org/10.1093/biolre/ioaf117","url":null,"abstract":"<p><p>A comparison of the effects of three fixatives - Neutral Buffered Formalin (NBF), modified Davidson's Fixative (mDF), and paraformaldehyde (PFA) - on human ovarian follicles reveals that mDF may better preserve follicle morphology.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590377","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":"An interview with Dr. Sally D. Perreault Darney.","authors":"Romana A Nowak","doi":"10.1093/biolre/ioaf152","DOIUrl":"https://doi.org/10.1093/biolre/ioaf152","url":null,"abstract":"","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590378","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 role for gut mycobiome and altered fungal-bacterial interactions in women with endometriosis.","authors":"Chandni Talwar, Ashirbad Guria, Kristi Hoffman, Scott Biest, Patricia Jimenez, Ramakrishna Kommagani","doi":"10.1093/biolre/ioaf148","DOIUrl":"https://doi.org/10.1093/biolre/ioaf148","url":null,"abstract":"<p><p>Endometriosis is a gynecological pathology prevalent in reproductive age women in which the inner uterine wall (endometrium) grows outside as ectopic lesions. The inflammation resulting from these growing implants closely associates with disease severity, causing chronic pain and infertility. Emerging studies have found altered bacterial communities in endometriosis and a causal role for gut bacteria in endometriosis. However, the role of the gut mycobiome i.e., the fungal component of the microbiome in endometriosis is a current knowledge gap that needs to be addressed. In this study, utilizing the stool samples from women with endometriosis, we found that the gut fungal communities are altered in women with endometriosis. By integrating the bacterial microbiota and studying the co-occurring relationships between fungi and bacteria, we identify the altered fungal-bacterial community interactions in endometriosis. In addition, we studied the microbial interactions with the host and identified the bacterial taxa as 'microbiome-associated host genetic variants' in endometriosis. By determining their interactions with fungi, we highlight the fungal taxa as underlying regulators of the disease. Experimentally, we demonstrate that the progression of endometriosis in mice is significantly impeded by the depletion of fungi, revealing a role for the gut mycobiome in endometriosis. Our results highlight the positive- and negative- co-abundance relationships shared between bacteria-fungi, bacteria-bacteria and microbes-host in the disease pathogenesis. These findings promise to stimulate future experimental research on the bacterial-fungal interactions that must be contemplated when designing microbiome-based therapeutic strategies using antifungal agents.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582901","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}
Luhan T Zhou, Dilan Gokyer, Krystal Madkins, Molly Beestrum, Daniel E Horton, Francesca E Duncan, Elnur Babayev
{"title":"The Effects of Heat Stress on the Ovary, Follicles and Oocytes: A Systematic Review†.","authors":"Luhan T Zhou, Dilan Gokyer, Krystal Madkins, Molly Beestrum, Daniel E Horton, Francesca E Duncan, Elnur Babayev","doi":"10.1093/biolre/ioaf150","DOIUrl":"10.1093/biolre/ioaf150","url":null,"abstract":"<p><p>Climate change is driving significant environmental changes with profound implications for human health, including fertility. Although the detrimental effects of heat on spermatogenesis are well-documented, the impact of elevated temperatures on ovaries and female fertility remains less explored. This systematic review evaluates the effects of elevated temperature exposures (heat stress, HS) on the ovary, follicles, and oocytes across a range of mammalian species. Drawing from both in vivo and in vitro studies, we synthesize findings that show HS can impair ovarian function by disrupting reproductive hormone profiles, reducing ovarian size and weight, altering ovarian histology, and inducing autophagy. At the cellular level, HS leads to increased granulosa cell apoptosis, impaired folliculogenesis, and decreased oocyte quality and developmental competence. However, inconsistencies across studies highlight the influence of experimental variation, including differences in species, timing, intensity, and duration of HS exposure. While many studies report detrimental effects, a few suggest possible adaptive responses under certain conditions. Finally, we review emerging interventions, including antioxidants, hormone supplementation, and bioactive compounds, that aim to counteract HS-related reproductive damage. Despite progress, further research is urgently needed to define conserved molecular pathways, optimize experimental models, and inform clinical strategies to protect fertility and reproductive lifespan in a warming world.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582903","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":"Human extravillous trophoblast invasion and migration are impeded by excessive miR-26a-5p: dysregulated actin cytoskeleton in extravillous trophoblasts during early-onset severe preeclampsia†.","authors":"Yuanke Zheng, Heng Liang, Hongyue Li, Tianfei Feng, Xiaohe Lei, Haotian Lu, Liang Wu","doi":"10.1093/biolre/ioaf151","DOIUrl":"https://doi.org/10.1093/biolre/ioaf151","url":null,"abstract":"<p><p>MiRNAs play crucial roles in the pathogenesis of preeclampsia (PE). In our previous study, miR-26a-5p was identified as one of the seven miRNAs whose levels were elevated in plasma samples from women with pregnancies complicated by severe PE (sPE). Defects in human extravillous trophoblast (EVT) invasion and migration contribute to the pathogenesis of early-onset PE; however, the effects of miR-26a-5p on these processes remain unclear. In this study, an increase in miR-26a-5p levels in plasma and placenta samples from pregnancies complicated by early-onset sPE was first confirmed. A progressive decrease in miR-26a-5p expression during the differentiation of cytotrophoblast (CTs) into invasive EVTs within the trophoblast columns (TCs) was revealed by fluorescence in situ hybridization. Mimic and inhibitor of miR-26a-5p significantly suppressed or promoted, respectively, the invasion and migration of HTR-8/SVneo cells and the outgrowth of primary EVTs derived from placental villous explants. Actin related protein 2/3 complex subunit 3 (ARPC3) was identified as a direct target of miR-26a-5p, and knockdown of ARPC3 mimicked the effects of miR-26a-5p on HTR-8/SVneo cell invasion/migration and explant EVT outgrowth. Conversely, ectopic expression of ARPC3 alleviated the suppressive effects of miR-26a-5p overexpression on HTR-8/SVneo cell invasion and migration. Disruption of actin cytoskeletal organization was observed following ARPC3 knockdown, leading to a significant transformation of lamellipodia to filopodia at the leading edges of cells, which eventually impeded directional EVT invasion and migration. Thus, dysregulated actin cytoskeletal organization mediated by the miR-26a-5p/ARPC3 axis may contribute to the pathogenesis of early-onset sPE by impairing EVT invasion and migration.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582902","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":"Relevance in updating the Warnock report banner. A review of Franklin & Jackson (2024). The 14 day rule and human embryo research.","authors":"Marta Reguera Cabezas","doi":"10.1093/biolre/ioaf145","DOIUrl":"https://doi.org/10.1093/biolre/ioaf145","url":null,"abstract":"<p><p>In The 14-Day Rule and Human Embryo Research, the reader will find a journey through the 1980s and 1990s, on the governance of human embryo research. At this time, what would be the most important international standard in this field was promulgated, limiting human embryonic development in vitro for research to 14 days. However, it should not be forgotten that this limit of development prevented any research in post-implantation stages, for example, in gastrulation and early organogenesis. This has led to a great lack of knowledge about the mechanisms that regulate cell differentiation and morphogenesis during the post-implantation stages. This rule has recently been challenged by scientific advances in the need to decipher the mechanisms of cell differentiation, with a matter of great interest to the field of regenerative medicine. This has led to the creation of human embryos derived from stem cells, which serve as models for the study of these unknown stages. Some authors and scientific societies propose increasing this limit to 28 days and leave open the possibility of new interdisciplinary debates on the legislative improvements that may be necessary at the present time.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574796","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}