Biology of Reproduction最新文献

{"title":"The downregulation of FKBP5 contributes to the pathogenesis of adenomyosis and is associated with impaired endometrial receptivity†.","authors":"Meng Wang, Yungai Xiang, Dan Zhang, Xujing Geng, Xiting Han, Peipei Guo, Le Zhang, Li Tan","doi":"10.1093/biolre/ioaf126","DOIUrl":"https://doi.org/10.1093/biolre/ioaf126","url":null,"abstract":"<p><p>Adenomyosis is characterized by the infiltration of endometrial glands and stroma into the myometrium which affects about 35% women at reproductive age. Women affected by adenomyosis always experience issues such as defective decidualization, reduced endometrial receptivity, disrupted embryo-maternal communication, and challenges with implantation. However, the underlying mechanism remains obscure. We analyzed three gene expression profiling datasets (GSE244236, GSE190580 and GSE157718) and identified that FKBP5 was significantly reduced in endometrium from patients with adenomyosis. Primary endometrial stromal cells (ESCs) from patients had increased proliferation, reduced apoptosis and elevated migration capacity. Knockdown FKBP5 in ESCs upregulated proliferation, repressed apoptosis, and impaired the secretion of prolactin and IGFBP-1 during in vitro decidualization. Meanwhile, repressing FKBP5 in ESCs promoted oxygen consumption rate, extracellular acidification rate, and ATP production. Mechanically, knockdown FKBP5 in ESCs activated AKT signaling by promoting its phosphorylation at Ser-473. FKBP5 was downregulated in patients with adenomyosis which contributed to impaired ESCs function and the process of decidualization providing a candidate target for adenomyosis treatment.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301063","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":"Developmental programming: mechanisms of early exposure to real-life chemicals in biosolids on offspring ovarian dynamics†.","authors":"Yiran Zhou, Katherine M Halloran, Michelle Bellingham, Richard G Lea, Neil P Evans, Kevin D Sinclair, Peter Smith, Vasantha Padmanabhan","doi":"10.1093/biolre/ioaf053","DOIUrl":"10.1093/biolre/ioaf053","url":null,"abstract":"<p><p>Female reproductive capacity is shaped by ovarian reserve and patterns of follicle development. Ovarian reserve depletion occurs by follicle activation and atresia, which are affected by environmental chemicals (ECs). Because humans are simultaneously exposed to hundreds of ECs, real-life exposure models are essential to assess patterns of atresia after EC exposure. Previous findings demonstrate maternal preconceptional and gestational EC exposure via biosolids increases activation rate and reduces primordial follicle pool in juvenile, but not adult sheep. We hypothesized that this shift involves changes in death and proliferative pathways that impact follicle atresia from juvenile to adult life. Ovaries were collected from juvenile (9.5 weeks) and adult (2.5 years) offspring from ewes grazed on biosolids-treated pasture (BTP) or inorganic fertilizer-treated pasture (Control). Follicular atresia was assessed through morphological characteristics and molecular death pathways, including expression of markers for apoptosis (CASP3), autophagy (LC3), ferroptosis (GPX4), and proliferation (Ki67). There were higher levels of apoptosis and autophagy, and lower proliferation, in juvenile BTP offspring compared to controls. In adult BTP offspring, apoptosis and proliferation were similar, autophagy was lower, and ferroptosis was higher compared to controls. Apoptosis was lower and ferroptosis was higher in adults than juveniles, regardless of treatment. Adult BTP offspring had lower autophagy and similar proliferation levels than juvenile BTP offspring. These findings suggest that lower autophagy and lack of decrease in proliferation contribute to normalization of activation rate and ovarian pool in BTP adult offspring and supportive of lasting impacts of gestational EC exposure on offspring follicular health.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1229-1242"},"PeriodicalIF":3.1,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690932","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":"Interferon tau-dependent and -independent changes in the bovine corpus luteum of early pregnancy†.","authors":"Camilla H K Hughes, Adelaide C Hellmers, M Isabel da Silva, Troy L Ott, Joy L Pate","doi":"10.1093/biolre/ioaf044","DOIUrl":"10.1093/biolre/ioaf044","url":null,"abstract":"<p><p>The effect of interferon tau (IFNT) on the uterus is critical for maternal recognition of pregnancy in ruminants, while its direct role in luteal function is less well understood. To address this, we performed two experiments. In Experiment 1, cattle received intrauterine infusions of either: bovine serum albumin (BSA; vehicle) or vehicle with IFNT from Days 14 to 16 of the estrous cycle or vehicle with IFNT from Days 14 to 19 or vehicle with IFNT from Days 14 to 19 with pregnancy associated glycoprotein (PAG) from Days 17 to 19. Corpora lutea (CL) were collected on Day 17 or 20 and RNAseq was performed. In Experiment 2, cultured luteal steroidogenic cells from cyclic (Days 10-12) cattle were treated with IFNT and RNAseq was performed. Treatment with IFNT resulted in luteal changes (in vivo: 130 transcripts; in vitro: 2981 transcripts), while addition of PAG resulted in 13 changed transcripts. Only 31% of the genes that changed in the CL during early pregnancy (Hughes et al., 2020) were regulated by IFNT; these were antiviral and immune regulators. In contrast, 50% of the genes that changed during early pregnancy were not regulated by IFNT and were associated with cellular proliferation and extracellular matrix organization. The remaining 19% of genes were not conclusively identified as either IFNT regulated or non-regulated. This suggests that the temporal changes in the CL during early pregnancy are only partially regulated by IFNT, drawing into question identities of other luteal regulators or the effect of age of CL.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1213-1228"},"PeriodicalIF":3.1,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143583800","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":"Exposure of bovine granulosa cells to lipopolysaccharide reduces progesterone secretion during luteinization†.","authors":"Zachary K Seekford, Stephanie E Wohlgemuth, I Martin Sheldon, John J Bromfield","doi":"10.1093/biolre/ioaf055","DOIUrl":"10.1093/biolre/ioaf055","url":null,"abstract":"<p><p>Uterine disease reduces fertility in dairy cows and is caused by pathogenic bacteria. During disease, lipopolysaccharide accumulates in follicular fluid and triggers granulosa cell inflammation via the Toll-like receptor 4 pathway. Follicle growth and plasma estradiol are reduced in cows with uterine disease, and treatment of bovine granulosa cells with lipopolysaccharide reduces cytochrome P450 family 19 subfamily A member 1 (CYP19A1) expression and estradiol synthesis. It is unclear whether the effects of lipopolysaccharide on the steroidogenic capacity of granulosa cells persist in cells during luteinization. We hypothesized that acute exposure of granulosa cells to lipopolysaccharide would alter progesterone synthesis during luteinization. Here, we demonstrate that acute exposure of granulosa cells to lipopolysaccharide reduces progesterone synthesis during a 9-day period of luteinization after lipopolysaccharide treatment. We show that exposure of granulosa cells to lipopolysaccharide does not alter the gene expression of steroidogenic acute regulatory protein (STAR), hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 (HSD3B1), or cytochrome P450 family 11 subfamily A member 1 (CYP11A1), or cellular respiration during luteinization. However, acute exposure of granulosa cells to lipopolysaccharide reduces the abundance of intracellular lipid, mitochondria density, and cholesterol uptake during luteinization, suggesting a potential mechanism of altered steroidogenesis after acute inflammation. Collectively, these findings show that exposure of granulosa cells to lipopolysaccharide reduces progesterone synthesis during luteinization, which is associated with altered lipid droplets and mitochondria accumulation required for steroidogenesis. Perturbations to granulosa cell physiology during uterine disease may have prolonged effects on ovarian function that contribute to reduced fertility of cows. Understanding the effects of uterine disease on corpus luteum function after disease resolution can help explain disease associated subfertility in cattle.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1243-1255"},"PeriodicalIF":3.1,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662105","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":"Establishing the baseline: understanding follicle activation morphometrics in multiple mammalian species†.","authors":"Hana Kubo, Christopher J McCauley, Mary B Zelinski, Monica M Laronda","doi":"10.1093/biolre/ioaf059","DOIUrl":"10.1093/biolre/ioaf059","url":null,"abstract":"<p><p>Folliculogenesis encompasses many stages as the somatic granulosa and theca cells support oocytes through growth and maturation. A novel follicle stage, between primordial and transitional stages, was identified in mice and defined as \"zip.\" Like all other follicle stages, the \"zip\" stage is characterized by its granulosa cell morphology. The \"wedge\" GC morphology in zip follicles is predicted to be the first granulosa cell division, marking the transition from squamous to cuboidal morphology. Here, zip and transitional stages were identified in histological sections of porcine, bovine, rhesus monkey, and human ovaries. Several growth dynamics characterized at these follicle stages were conserved between species. Oocyte diameter and area increased between the primordial and transitional stages in the porcine ovary and between the primordial and primary stages in the rhesus monkey ovary but appeared unchanged in bovine and human ovaries. In all species except for pigs, granulosa cell number and height increased at stages earlier than observed changes in the oocyte. Furthermore, there were differences in the percentage of zip and transitional follicle stages present in the cortical region across species. This implies that there may be species-dependent activation and growth mechanisms that require further study. The parameters defined here for identifying and characterizing the zip and transitional follicle stages across species can act as a tool for measuring factors that perturb or induce primordial follicle activation or effect follicle morphometric parameters in support of future innovations for fertility preservation and restoration.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1123-1133"},"PeriodicalIF":3.1,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690936","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":"Loss of N-6 adenine-specific DNA methyltransferase 1 leads to meiotic prophase abnormalities and male sub-fertility in mice†.","authors":"Yuru Luo, Shuang Liu, Yuan Fang, Hongyu Su, Jinling Dong, Baochang Lai, Zhen Wang, Juan Yang, Donghong Zhang, Yidong Wang","doi":"10.1093/biolre/ioaf052","DOIUrl":"10.1093/biolre/ioaf052","url":null,"abstract":"<p><p>Mammalian sexual reproduction critically relies on the generation of haploid gametes following a specialized cell division process known as meiosis. Here, we demonstrate that N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) plays a crucial role in the progression of meiosis during spermatogenesis, as follows. N6AMT1 was expressed in germ cells throughout the entire process of spermatogenesis, with a peak in mRNA levels in spermatocytes at the prophase I stage of meiosis. Germ cell-specific deletion of N6amt1 in mice resulted in male subfertility as well as a significant reduction in sperm count. Notably, N6amt1-null spermatocytes exhibited meiotic arrest at prophase I and extensive apoptosis. Chromosome spreading assays revealed that N6amt1 loss impaired meiotic sex chromosome inactivation (MSCI) and delayed DNA double-strand break (DSB) repair. Correspondingly, transcriptomic analysis identified a substantial increase in transcript levels for genes mapping to sex chromosomes in N6amt1-null mutants, consistent with disruptions in MSCI. Moreover, N6AMT1 deficiency led to a significant upregulation in the steady-state mRNA levels of genes involved in the p53 pathway and functionally activated p53 signaling. Through integrated analysis of data from single-cell RNA sequencing (RNA-seq) and bulk RNA-seq experiments, we found that knockout of N6amt1 primarily affected the transcriptomic profiles of normal pachytene spermatocytes. Taken together, our findings demonstrate that N6AMT1 is required for quantitatively normal male fertility in mice and involved in the molecular mechanisms for meiotic progression during spermatogenesis, including MSCI and DSB repair.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1289-1303"},"PeriodicalIF":3.1,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613345","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":"Delayed blastocyst development is associated with altered metabolism and proteome in male and female bovine embryos†.","authors":"Kyle J Fresa, Ming-Hao Cheng, Keira Y Larson, Alexandra A Crook, Anthony J Saviola, Raul A Gonzalez-Castro, Thomas W Chen, Elaine M Carnevale","doi":"10.1093/biolre/ioaf058","DOIUrl":"10.1093/biolre/ioaf058","url":null,"abstract":"<p><p>Developmentally delayed embryos are associated with reduced implantation potential and live birth rates; however, inherent causes of delayed development are not well understood. Metabolism during preimplantation development is responsible for the production of energy and biosynthetic material to support growth, and disturbances to these pathways can reduce embryo viability. The present study utilized electrochemical microsensors to determine differences in rates for oxygen consumption, extracellular acidification, and hydrogen peroxide production between normal and slow-growing, male and female bovine blastocysts. In addition, pooled samples of blastocysts were subjected to proteomic analysis to determine differences in the abundance of proteins associated with metabolism between the sexes and developmental timing status. In comparison to blastocysts developing over a normal timespan, blastocysts forming 1-2 days later had a higher oxygen consumption rate, differences in abundance of electron transport complex proteins, and reduced abundance of biosynthetic enzymes when compared to blastocysts developing during a normal timeline. Embryo sex resulted in unique differences in metabolic enzyme abundance with potentially different contributions to delayed development. In addition, male and female blastocysts had differential protein abundances, indicating differences in metabolic pathway activity. Therefore, embryos that took longer to reach the blastocyst stage of development appeared to have an imbalance between energy production and biosynthetic activity, which could differentially impact male and female embryos.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1072-1085"},"PeriodicalIF":3.1,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668655","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":"Correction to: AURKA inhibits the decidualization of the eutopic endometrium in endometriosis through nuclear factor-κB p65.","authors":"","doi":"10.1093/biolre/ioaf106","DOIUrl":"10.1093/biolre/ioaf106","url":null,"abstract":"","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1304-1306"},"PeriodicalIF":3.1,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952790","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":"Morphological characterization of spermatogenesis and spermatogonial stem cells in Larimichthys crocea, a seasonal breeding teleost†.","authors":"Yinan Zhou, Yang Yang, Huan Ye, Lulu Mi, Weihua Hu, Dongdong Xu","doi":"10.1093/biolre/ioaf065","DOIUrl":"10.1093/biolre/ioaf065","url":null,"abstract":"<p><p>Seasonal spermatogenesis in fish is a complex and highly regulated process in which spermatogonial stem cells (SSCs) undergo a series of cellular changes to differentiate into mature sperm. In this study, we systematically described testicular development and identified thirteen different germ cell types throughout the reproductive cycle in large yellow croaker (Larimichthys crocea), a commercially important marine cultured fish in East Asia. Using a set of specific antibodies (VASA, PCNA, DMC1, NANOS2 and GSDF), we developed a high-throughput immunohistochemistry method to identify different types of spermatogenic cells, with a particular focus on distinguishing spermatogonial subtypes. VASA was strongly expressed in all four types of spermatogonia (As, Apr, Adiff, and B) and decreased progressively during spermatogenesis. DMC1 exhibited distinct expression patterns in different spermatocytes subtypes, and GSDF was highly expressed in somatic cells surrounding type A spermatogonia. Particularly, NANOS2 was highly specific to As and Apr spermatogonia, supporting their role as SSC candidates. By morphological observation and co-staining of VASA and PCNA, we found that As spermatogonia exhibited dynamic development characteristics during the annual reproductive cycle. These findings provide a valuable tool for reproductive studies and potential applications in surrogate reproduction through SSCs transplantation in teleost fish.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1185-1199"},"PeriodicalIF":3.1,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963871","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":"SRA deficiency induces follicular dysplasia by disrupting the hypothalamic Kisspeptin-GPR54 system in mice†.","authors":"Jing Jin, Xinhui Kou, Xinzhe Wang, Xue Yun, Yinyin Ding, Keshu Cai, Yongning Zhai, Huifang Zhou","doi":"10.1093/biolre/ioaf049","DOIUrl":"10.1093/biolre/ioaf049","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate how steroid receptor RNA activator (SRA) regulates follicular development in mice.</p><p><strong>Methods: </strong>Systemic SRA knockout mice were introduced. SRA expression was reinstated in the anteroventral periventricular nucleus (AVPV) of the hypothalamus using lentiviral vectors. Subsequently, the estrous cycle, serum hormone levels, follicle development, and hypothalamic kisspeptin expression in mice were assessed. Kiss1 promoter activity was tested with a fluorescent reporter system in Neuro-2a cells.</p><p><strong>Results: </strong>SRA deficiency caused a shift to shorter metestrus and longer diestrus phases, reduced numbers of large antral and preovulatory follicles, increased formation of atretic cyst-like follicles, lowered serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2), and decreased expression of hypothalamic AVPV-kisspeptin in mice. The reinstatement of SRA expression in the AVPV nucleus normalized kisspeptin expression, hormone levels, and follicle development. In Neuro-2a cells, SRA increased Kiss1 transcription upon E2 treatment, a response that was nullified by the estrogen receptor alpha (ERα) inhibitor.</p><p><strong>Conclusion: </strong>SRA enhances ERα-mediated Kiss1 transcription in the AVPV nucleus to control the kisspeptin-GPR54 system in the hypothalamus, essential for regulating ovulation through the hypothalamus-pituitary-ovary axis.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1114-1122"},"PeriodicalIF":3.1,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584501","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}