Biology of Reproduction最新文献_第6页

Establishing the baseline: understanding follicle activation morphometrics in multiple mammalian species†. 建立基线：了解多种哺乳动物物种的卵泡激活形态计量学。

IF 3.1 2区生物学

Biology of Reproduction Pub Date : 2025-06-15 DOI: 10.1093/biolre/ioaf059

Hana Kubo, Christopher J McCauley, Mary B Zelinski, Monica M Laronda

{"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":"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.","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191627/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Loss of N-6 adenine-specific DNA methyltransferase 1 leads to meiotic prophase abnormalities and male sub-fertility in mice†. N-6腺嘌呤特异性DNA甲基转移酶1的缺失导致小鼠减数分裂前期异常和雄性低生育能力。

IF 3.1 2区生物学

Biology of Reproduction Pub Date : 2025-06-15 DOI: 10.1093/biolre/ioaf052

Yuru Luo, Shuang Liu, Yuan Fang, Hongyu Su, Jinling Dong, Baochang Lai, Zhen Wang, Juan Yang, Donghong Zhang, Yidong Wang

{"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":"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.","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}

引用次数: 0

Correction to: AURKA inhibits the decidualization of the eutopic endometrium in endometriosis through nuclear factor-κB p65. 更正：AURKA通过核因子-κB p65抑制子宫内膜异位症异位子宫内膜的去个体化。

IF 3.1 2区生物学

Biology of Reproduction Pub Date : 2025-06-15 DOI: 10.1093/biolre/ioaf106

引用次数: 0

Delayed blastocyst development is associated with altered metabolism and proteome in male and female bovine embryos†. 在雄性和雌性牛胚胎中，囊胚发育延迟与代谢和蛋白质组改变有关。

IF 3.1 2区生物学

Biology of Reproduction Pub Date : 2025-06-15 DOI: 10.1093/biolre/ioaf058

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

{"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":"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.","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191644/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Morphological characterization of spermatogenesis and spermatogonial stem cells in Larimichthys crocea, a seasonal breeding teleost†. 季节性繁殖硬骨鱼（Larimichthys crocea）精子发生和精原干细胞的形态学特征。

IF 3.1 2区生物学

Biology of Reproduction Pub Date : 2025-06-15 DOI: 10.1093/biolre/ioaf065

Yinan Zhou, Yang Yang, Huan Ye, Lulu Mi, Weihua Hu, Dongdong Xu

{"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":"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.","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}

引用次数: 0

SRA deficiency induces follicular dysplasia by disrupting the hypothalamic Kisspeptin-GPR54 system in mice†. SRA缺乏通过破坏小鼠下丘脑Kisspeptin-GPR54系统诱导卵泡发育不良。

IF 3.1 2区生物学

Biology of Reproduction Pub Date : 2025-06-15 DOI: 10.1093/biolre/ioaf049

Jing Jin, Xinhui Kou, Xinzhe Wang, Xue Yun, Yinyin Ding, Keshu Cai, Yongning Zhai, Huifang Zhou

{"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":"Purpose: To investigate how steroid receptor RNA activator (SRA) regulates follicular development in mice.Methods: 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.Results: 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.Conclusion: 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.","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}

引用次数: 0

Microplastics and impaired male reproductive health-exploring biological pathways of harm: a narrative review. 微塑料和男性生殖健康受损-探索危害的生物学途径：叙述回顾。

IF 3.1 2区生物学

Biology of Reproduction Pub Date : 2025-06-15 DOI: 10.1093/biolre/ioaf054

Naina Kumar, Mishu Mangla

{"title":"Microplastics and impaired male reproductive health-exploring biological pathways of harm: a narrative review.","authors":"Naina Kumar, Mishu Mangla","doi":"10.1093/biolre/ioaf054","DOIUrl":"10.1093/biolre/ioaf054","url":null,"abstract":"Introduction: Microplastics, pervasive environmental pollutants, have emerged as significant health hazards with growing evidence linking them to impaired male reproductive health. Microplastics can enter the human body through ingestion, inhalation, and dermal absorption and, once internalized, can induce oxidative stress, inflammation, endocrine disruption, and cellular damage leading to impaired male reproductive health. The present narrative review explores the biological pathways through which microplastics impair male reproductive health, focusing on their direct and systemic effects.Methodology: A comprehensive literature search spanning up to February 2025 was conducted across electronic databases, including PubMed, Scopus, Web of Science, and Google Scholar. Search terms such as \"microplastic exposure,\" \"male infertility,\" \"male reproductive health,\" \"oxidative stress,\" \"endocrine disruption,\" \"spermatogenesis,\" \"inflammation,\" and \"reproductive toxicity\" were employed to identify relevant studies published in peer-reviewed journals, books, and reputable conference proceedings. Inclusion criteria were limited to articles written in English that focused on the biological pathways linking MP exposure to impaired male reproductive health. Priority was given to review articles, original research papers, and meta-analyses. Extracted information was systematically organized to provide a narrative synthesis.Conclusion: Current evidence suggests that microplastics may impair male reproductive health through mechanisms like oxidative stress, hormonal disruption, inflammation, and cellular damage. However, the lack of human studies highlights the urgent need for robust research to clarify their impact on human male infertility. Furthermore, this review underscores the necessity for continued research to elucidate molecular mechanisms, inform preventative strategies, and guide regulatory policies addressing microplastic pollution and its health implications.","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1028-1038"},"PeriodicalIF":3.1,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668747","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}

引用次数: 0

Kynurenine, a derivative of tryptophan, inhibits progesterone biosynthesis in porcine granulosa luteal cells through Aryl hydrocarbon receptor-mediated downregulation of GATA-binding protein 4, 6, and CCAAT/enhancer-binding protein beta†. 犬尿氨酸是色氨酸的衍生物，通过ahr介导的GATA4、GATA6和CEBPB的下调抑制猪黄体颗粒细胞中的孕酮生物合成。

IF 3.1 2区生物学

Biology of Reproduction Pub Date : 2025-06-15 DOI: 10.1093/biolre/ioaf031

Shiying Liao, Jinhua Cheng, Weimin Zhao, Chaohui Dai, Yanfeng Fu, Bixia Li, Yanfei Deng, Hui Li

{"title":"Kynurenine, a derivative of tryptophan, inhibits progesterone biosynthesis in porcine granulosa luteal cells through Aryl hydrocarbon receptor-mediated downregulation of GATA-binding protein 4, 6, and CCAAT/enhancer-binding protein beta†.","authors":"Shiying Liao, Jinhua Cheng, Weimin Zhao, Chaohui Dai, Yanfeng Fu, Bixia Li, Yanfei Deng, Hui Li","doi":"10.1093/biolre/ioaf031","DOIUrl":"10.1093/biolre/ioaf031","url":null,"abstract":"Kynurenine (KYN) is a primary tryptophan derivative found in the human body and fermented foods. Previous studies have shown that KYN is an aryl hydrocarbon receptor (AHR) agonist and is important in regulating various physiological activities, including female reproduction. Progesterone is a vital steroid hormone that facilitates embryo implantation and maintains pregnancy. However, whether KYN affects its biosynthesis remains unclear. To gain understanding, in vitro luteinized porcine granulosa luteal (pGL) cells were treated with KYN. The results showed that KYN disrupted progesterone biosynthesis by decreasing the expression of steroidogenic acute regulatory protein (STAR) and 3beta-hydroxysteroid dehydrogenase (HSD3B) in pGL cells. In addition, the expression of three transcription factors of STAR and HSD3B (GATA4, GATA6, and CEBPB) decreased after KYN treatment. Furthermore, the AHR blockade results showed comparable effects to those of KYN treatment, and subsequent knockdown experiments confirmed these results. These findings suggest that KYN inhibits progesterone biosynthesis in pGL cells by downregulating GATA4, GATA6, and CEBPB expression through AHR. Thus, our results showed for the first time a previously unknown connection between KYN and progesterone biosynthesis.","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1200-1212"},"PeriodicalIF":3.1,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381668","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}

引用次数: 0

Diverse roles of stress-responsive RNP granules in oogenesis and infertility. 应激反应性RNP颗粒在卵子发生和不孕症中的多种作用。

IF 3.1 2区生物学

Biology of Reproduction Pub Date : 2025-06-15 DOI: 10.1093/biolre/ioaf057

M Rebecca Glineburg, Carolee Nguyen

{"title":"Diverse roles of stress-responsive RNP granules in oogenesis and infertility.","authors":"M Rebecca Glineburg, Carolee Nguyen","doi":"10.1093/biolre/ioaf057","DOIUrl":"10.1093/biolre/ioaf057","url":null,"abstract":"Effectively responding to cellular stress (e.g., nutrient deprivation, oxidative stress) is essential for cell and organismal survival. A protective mechanism is especially critical in developing oocytes, where a prolonged quiescent state and the inability to divide render oocytes highly susceptible to accumulating stress that can result in cell death if unaddressed. Despite the common view that stress granules are the primary stress-responsive ribonucleoprotein granule, accumulating evidence shows that in ovaries, other ribonucleoprotein granules also uniquely mediate gene regulation in response to stress. Here, we review recent insights into ribonucleoprotein granule dynamics and ribonucleoprotein granule protein function during stress in the context of oogenesis among both invertebrates and vertebrates, with an emphasis on insights from Drosophila and mice. We also discuss roles for stress-responsive ribonucleoproteins in maintaining stem cell populations and complicating fertility treatments. By exploring how stress-induced ribonucleoprotein dynamics can impact oogenesis, both positively and negatively, we can better understand how stress contributes to reduced fecundity and infertility. We conclude by offering key research questions that can drive the next generation of insights.","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1039-1053"},"PeriodicalIF":3.1,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668733","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}

引用次数: 0

The roles of AKT isoforms in decidualization and embryo implantation using a Progesterone Receptor-Cre mouse model†. AKT同种异构体在PGR-Cre小鼠模型的去个体化和胚胎着床中的作用。

IF 3.1 2区生物学

Biology of Reproduction Pub Date : 2025-06-15 DOI: 10.1093/biolre/ioaf062

Pascal Adam, François Fabi, Sophie Parent, Léa-Isabelle Renaud, Monique Cadrin, Eric Asselin

{"title":"The roles of AKT isoforms in decidualization and embryo implantation using a Progesterone Receptor-Cre mouse model†.","authors":"Pascal Adam, François Fabi, Sophie Parent, Léa-Isabelle Renaud, Monique Cadrin, Eric Asselin","doi":"10.1093/biolre/ioaf062","DOIUrl":"10.1093/biolre/ioaf062","url":null,"abstract":"Implantation is a complex process requiring a prepared, receptive endometrium, reliant on synchronized decidualization of stromal cells. During this process, cell proliferation and apoptosis are tightly regulated by signaling factors, including the survival and proliferation of the PI3K/AKT pathway. The three AKT isoforms each play distinct physiological roles, but their specific functions in endometrial cell survival and apoptosis remain unclear. We hypothesize that for successful implantation, each AKT isoform has distinct roles in the endometrium during decidualization, which varies throughout the process. To explore this, we developed a unique PGR-Cre tissue-specific mouse model with single and combined knockouts (KO) of each AKT isoform. Using artificial decidualization during pseudopregnancy and normal gestation, we investigated the specific activity of each AKT isoform and their downstream targets to assess the role of AKT pathway. Our results showed that the AKT1-2 KO genotype failed to decidualize during pseudopregnancy and exhibited a reduced number of implantation sites. Interestingly, AKT3 was hyperphosphorylated in the AKT1-2 KO mice and emerged as the primary isoform active throughout decidualization, specifically signaling through GSK3B. This study suggests distinct yet partially redundant roles for AKT1 and AKT2 during decidualization and embryo implantation. We propose that the AKT pathway plays significant role in fertility, and a deeper understanding of its involvement in decidualization could lead to improved strategies for addressing fertility issues. These findings highlight the importance of AKT activity in the cellular and molecular regulation of mouse fertility.","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1134-1147"},"PeriodicalIF":3.1,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717855","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}

引用次数: 0