Biology of Reproduction最新文献

{"title":"Correction: Follicle identification in primate ovaries via machine learning.","authors":"","doi":"10.1093/biolre/ioag215","DOIUrl":"10.1093/biolre/ioag215","url":null,"abstract":"","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058206","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. Peter Hansen.","authors":"Romana A Nowak","doi":"10.1093/biolre/ioag212","DOIUrl":"https://doi.org/10.1093/biolre/ioag212","url":null,"abstract":"","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036515","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":"Progesterone regulates lipid synthesis and secretion in bovine uterine epithelial cells.","authors":"Arpna Sharma, Diego Hernández-Saavedra, Matthew Dean","doi":"10.1093/biolre/ioag213","DOIUrl":"https://doi.org/10.1093/biolre/ioag213","url":null,"abstract":"<p><p>Uterine secretions consist of a mixture of nutrients that support the growth of the implanted embryo. Our previous data showed that progesterone increased NADPH production in bovine uterine epithelial (BUTE) cells, leading us to hypothesize that progesterone modulates lipid synthesis and secretion. R. Untargeted lipidomics of control and progesterone-treated (10 μM) BUTE cells and conditioned media detected 1,607 lipid species across 14 distinct lipid subclasses. In conditioned media, progesterone significantly decreased 3 lipid species. Conversely, progesterone increased the levels of 130 lipid species, increasing the concentrations of phosphatidylcholines, oxidized triglycerides, and ether triglycerides. Unbiased lipid clustering analysis in the BUTE cells showed that progesterone produced widespread lipid alterations, significantly increasing 34 and decreasing 19 lipid species. This was validated in BUTE cells in vitro, whereby progesterone increased intracellular triglyceride levels and lipid droplets. Immunohistochemistry of endometrial biopsies collected from the cow uterus on days 1 and 11 of the cycle showed that the lipid storage and esterification enzymes LPIN1 and DGAT2 were significantly higher in the glandular epithelium on day 11. These results suggest that progesterone increases lipid synthesis and secretion by the uterine epithelium when progesterone concentrations are high, such as in the luteal phase or early pregnancy.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036477","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":"Ovarian fibrosis as a common mechanism of infertility.","authors":"Caroline J Aitken, David A Landry","doi":"10.1093/biolre/ioag214","DOIUrl":"https://doi.org/10.1093/biolre/ioag214","url":null,"abstract":"<p><p>Female fertility has long been explained through observation of the ovarian follicle: the number of residing follicles and the quality of the oocyte. This review argues that the tissue surrounding those follicles involved in regulating cyclical ovarian remodelling is an additional contributor to female subfertility. Ovarian fibrosis, the accumulation of extracellular matrix with stromal stiffening and inflammation, was historically viewed as a passive consequence of aging or injury. Here, we present evidence that this phenomenon may be an active constraint on fertility, altering the biomechanical environment that manages follicle activation, ovulation, and oocyte quality. Although reproductive aging, premature ovarian insufficiency, polyendocrine metabolic ovarian syndrome, obesity, endometriosis, chronic psychological stress, and treatment/environment-induced ovarian injury have different underlying causes, all reach a similar fibrotic state. Strong causal evidence comes from in vitro hydrogel studies isolating stiffness from all other variables, where stiff matrices inhibit follicle growth, survival and quality. Despite this highly fibrotic morphology impacting maturation of follicles, pre-clinical and human studies have shown the efficacy of antifibrotic drugs in restoring follicular growth. Further, in early human trials, antifibrotic finerenone yields mature oocytes and embryos in women with premature ovarian insufficiency. While the current focus in standard infertility treatment aims to improve follicle and hormone health, fibrosis may be reversible and preventable, making it a candidate therapeutic target that could complement existing treatments. However, key gaps remain: no standardized measure of ovarian fibrosis, uncertain rodent-to-human translation, and no study linking fibrosis measurement to a fertility outcome in human patients.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036494","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":"CXCL12/CXCR4 signaling coordinates trophoblast, immune, vascular, and metabolic programming during early placentation in sheep.","authors":"Ryan Ashley, Makayla Mullins, Shaylie Salopek, Kyla Saucedo, Ema Alvarez, Monet Hunt, Samantha Baez, Niklas Kronlein, Kassandra Valdez, Lauren Butler, Kate Ropp","doi":"10.1093/biolre/ioag211","DOIUrl":"https://doi.org/10.1093/biolre/ioag211","url":null,"abstract":"<p><p>Successful placentation requires coordinated regulation of trophoblast differentiation, immune tolerance, vascular remodeling, and nutrient transport during the peri-implantation period. The chemokine ligand CXCL12 and its receptor CXCR4 are expressed at the fetal-maternal interface and implicated in trophoblast migration, immune regulation, and angiogenesis, but their in vivo role in early placental functional development remains unclear. The objective of this study was to determine whether suppression of CXCL12/CXCR4 signaling during implantation alters placental programming in sheep. Ewes received intrauterine infusion of CXCR4 antagonist AMD3100 from Day 12-19 of pregnancy, and tissues were collected on Day 20. Pregnancy rates were not affected by treatment; however, pregnancy-associated glycoprotein abundance was increased in treated ewes, indicating altered trophoblast differentiation. Inhibiting CXCR4 reduced expression of angiogenic factors including vascular endothelial growth factor A, placental growth factor, fms-like tyrosine kinase-1, and angiopoietin-1 in endometrium, consistent with impaired vascular development. Suppression of CXCR4 also shifted immune signaling toward a pro-inflammatory profile, with increased interferon-gamma and interleukin-12 and decreased transforming growth factor beta. In addition, expression of glucose and amino acid transporters, including SLC2A1, SLC2A3, SLC38, and SLC7 family members, was altered in fetal membranes and endometrium, accompanied by increased autophagy marker LC3B-II, suggesting metabolic stress. These findings demonstrate that CXCL12/CXCR4 signaling is not required for conceptus attachment but is important for coordinated development of vascular, immune, and metabolic pathways during early placentation. Disruption of this axis produces molecular changes consistent with placental insufficiency, supporting a central role for CXCL12/CXCR4 in establishing functional placental capacity.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036499","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":"Conceptus attachment coincides with initiation of an anti-inflammatory cytokine profile in the pig endometrium.","authors":"Günter P Wagner, Thainá Minela, Alexandria Ross, Jan Engelhardt, Fuller W Bazer, Gregory A Johnson","doi":"10.1093/biolre/ioag208","DOIUrl":"https://doi.org/10.1093/biolre/ioag208","url":null,"abstract":"<p><p>Blastocyst implantation is associated with quasi-inflammatory reactions in the endometrium, which are resolved during the establishment of the definitive placenta. Quasi-inflammatory processes have also been documented in pregnant pigs, even though the blastocyst only attaches to, rather than implants into the endometrium. We asked what processes lead to the resolution of attachment-associated inflammation. In wound healing the transition towards an anti-inflammatory state includes the transition from M1 to M2 polarized macrophages. In order to determine whether this scenario applies also to the peri-attachment porcine uterus, we produced a series of bulk transcriptomes spanning days 13 to 25 of gestation. We found slower changes in the transcriptome between D20 and D25 than prior to D20, suggesting a turning point in pregnancy-related endometrial reprogramming. This period corresponds to the firm attachment of trophectoderm to the uterine epithelium and the cessation of IFNG signaling from the blastocyst. We found increased expression of genes implicated in resolution of inflammation and M2 polarization such as ARG1, MRC1, CD86, TGFb1 and IL10, and an increase in expression of HGPD, the enzyme metabolizing prostaglandins. While immunoreactivity for ARG1 was found in putative macrophages, other M2 markers were localized to non-immune cells: MRC1 in fibroblast-like stromal cells, CD86 on trophoblast cells, and IL10 in endometrial epithelia. CD86 undergoes trogocytosis into the luminal epithelium by D25. These results suggest that intrauterine immune regulation is decoupled from that of the rest of the body by engaging non-immune cells as anti-inflammatory mediators during the peri-attachment period of porcine pregnancy.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023820","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":"Phenotypic Heterogeneity During Sperm Capacitation: A Compositional Analysis.","authors":"Benjamin M Brisard, Aishwarya P Halder, Aidan Charles, Amy L Ward, Maryam Asadi, David Hart, Debajit Bhowmick, Paul Vos, Cameron A Schmidt","doi":"10.1093/biolre/ioag207","DOIUrl":"https://doi.org/10.1093/biolre/ioag207","url":null,"abstract":"<p><p>Mammalian sperm must undergo capacitation, a process marked by substantial phenotypic heterogeneity among sperm. How heterogeneity relates to fertilizing potential remains unresolved, in part because sperm subpopulations are typically analyzed independently despite being intrinsically interdependent. We combine flow cytometry with statistical modeling to quantify how sperm subpopulation compositions respond to a range of capacitation signal intensity in vitro. Using cauda epididymal mouse sperm, we systematically varied extracellular bicarbonate and free calcium-key regulators of capacitation-and classified millions of individual cells into four irreversible physiological states. We show that bicarbonate and calcium interact nonlinearly to redistribute sperm across these subpopulations, revealing responses that would be otherwise obscured in measurements lacking single-cell resolution. Elevated intracellular calcium was associated with increased cell death, while the highest proportions of live, acrosome-reacted sperm occurred under relatively low extracellular calcium conditions. We then applied a hierarchical Dirichlet-multinomial regression model that accounts for multinomial sampling noise and between-male variability, yielding posterior probability surfaces that describe how sperm subpopulations reallocate across functional states as signaling conditions change. We then tested the model predictions using IVF and found that the proportion of live, acrosome reacted sperm was not predictive of early embryonic developmental success. Together, these results suggest that capacitation, though tightly regulated at the single cell scale, is a stochastic process shaped by structured phenotypic heterogeneity at the cell population scale. This framework provides a quantitative foundation for linking sperm subpopulation composition to measures of fertility competence.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023811","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":"DELE1 is dispensable for heat-stress-induced ISR during mouse spermatogenesis but has implications for lipid metabolism.","authors":"Yilan Teng, Mingxing Zhang, Zhicheng Wu, Zixuan Li, Deqiang Ding, Hongwen Zhu, Peng Dai","doi":"10.1093/biolre/ioag206","DOIUrl":"https://doi.org/10.1093/biolre/ioag206","url":null,"abstract":"","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015540","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":"The roles of the STAT3 signaling pathway in the establishment of endometrial receptivity and decidualization.","authors":"Hong Zhao, Zongyuan Zou, Yihua Yang","doi":"10.1093/biolre/ioag202","DOIUrl":"https://doi.org/10.1093/biolre/ioag202","url":null,"abstract":"<p><p>The establishment of endometrial receptivity is a fundamental prerequisite for successful embryo implantation and the maintenance of pregnancy. Decidualization, a critical process in the maturation of endometrial receptivity, is intimately linked to implantation success. The precise molecular regulation of both processes is essential for normal pregnancy outcomes. Within the endometrium, the activation of the transcription factor signal transducer and activator of transcription 3 (STAT3) exhibits strict temporal and spatial specificity. Its phosphorylation levels peak during the mid-secretory phase, aligning perfectly with the window of implantation, thereby establishing STAT3 as a primary indicator of endometrial receptivity. Activated by crucial cytokines-including leukemia inhibitory factor (LIF), interleukin (IL)-11, and epidermal growth factor (EGF)-STAT3 operates through the Janus kinase (JAK)/STAT signaling pathway. It regulates the functional maturation, adhesive capacity, and polarity remodeling of endometrial epithelial cells, creating an optimal environment for blastocyst attachment. Concurrently, STAT3 acts as a central regulator of decidualization by directly driving the proliferation and differentiation of endometrial stromal cells (ESCs) while maintaining the stability of the decidual microenvironment. Furthermore, STAT3 modulates the local immune milieu by orchestrating immune cell polarization and cytokine networks, providing essential immunological support. Conversely, dysregulation of the STAT3 signaling pathway leads to impaired endometrial receptivity and defective decidualization, contributing to adverse reproductive outcomes such as implantation failure and miscarriage. This review comprehensively highlights the pivotal regulatory functions of the STAT3 pathway in endometrial receptivity and decidualization, establishing a robust theoretical foundation for future basic research and targeted clinical strategies.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015625","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":"Multiscale Regulation of Meiotic Recombination in Mammals.","authors":"Najma Shaheen, Andrea Marton Menendez, Florencia Pratto","doi":"10.1093/biolre/ioag204","DOIUrl":"https://doi.org/10.1093/biolre/ioag204","url":null,"abstract":"<p><p>Meiotic recombination is a multilayered process that shapes genetic diversity while safeguarding genome stability. In mammals, the final distribution of crossovers and non-crossovers emerges from the integration of sequence-specific hotspot specification, chromosome architecture, replication timing, and crossover patterning mechanisms. PRDM9 directs most double-strand break formation to short (typically 1-2 kb), rapidly evolving hotspots by depositing histone marks and remodeling chromatin, whereas in PRDM9-independent contexts, breaks are redirected toward accessible promoters and CpG islands. Yet hotspot marking alone is insufficient: double-strand break formation requires assembly of the SPO11-TOPOVIBL catalytic machinery together with accessory proteins on the chromosome axis, linking recombination initiation to loop-axis organization. Broader regional biases are further imposed by meiotic replication timing, which favors early replicating domains. Downstream, only a small fraction of breaks matures into crossovers through ZMM-dependent stabilization, HEI10/RNF212-mediated dynamics, crossover interference, and the obligate crossover rule. These mechanisms result in sex-specific recombination landscapes, with structural differences in axis length and synapsis dynamics contributing to heterochiasmy. Disruption at any of these control layers can compromise homolog segregation and promote infertility, aneuploidy, recurrent pregnancy loss, or structural genomic disorders. Together, these findings support a hierarchical model in which meiotic recombination is best understood as the integrated output of DNA sequence, chromatin state, chromosome architecture, and choice of repair pathway-based patterning.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015530","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}