Reproduction最新文献

{"title":"IMPACT OF REAL-LIFE ENVIRONMENTAL EXPOSURES ON REPRODUCTION: Impact of human-relevant doses of endocrine-disrupting chemical and drug mixtures on testis development and function.","authors":"Nicole Mohajer, Martine Culty","doi":"10.1530/REP-24-0155","DOIUrl":"10.1530/REP-24-0155","url":null,"abstract":"<p><strong>In brief: </strong>Toxicological studies better resembling human exposures are needed to improve risk assessment. This review presents studies examining the impact of low-dose exposure to endocrine-disrupting chemical (EDC) mixtures, some combined with pharmaceuticals, on male reproduction in animal models and humans.</p><p><strong>Abstract: </strong>Exposure to EDCs and pharmaceuticals during development has been linked to reproductive dysfunction, reduced semen quality, and infertility. Research indicates that EDC mixtures, which are common in the modern environment, can pose significant risks that may not be fully assessed by studying individual compound toxicity, especially at environmentally relevant doses or concentrations. Understanding the contribution of chemical mixtures to male reproductive toxicity is crucial, given the increasing reliance on pharmaceuticals and pervasiveness of anthropogenic pollution. Recent studies on EDC effects have expanded to a more diverse range of microplastics, pesticides, antimicrobials, phytoestrogens, and pharmaceuticals, such as analgesics, which can collectively impact testicular function and fertility. Adverse outcomes observed across studies include reproductive tract malformations, decreased sperm count and motility, lowered testosterone, delayed-onset puberty, and possible causal effects, such as oxidative stress and altered gene expression. Still, limited data exist on combinations of environmental pollutants and pharmaceuticals with ED potential at human-relevant doses. This review of the recent literature aims to synthesize the toxicological impact of low-dose chemical mixtures on male reproductive health. Overall, humans are exposed to EDCs and drugs through various ways, necessitating an understanding of their concomitant effects on male reproductive health.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An attempt to search for the common cellular mechanism of ovulation across all metazoans.","authors":"Takayuki Takahashi, Katsueki Ogiwara","doi":"10.1530/REP-24-0184","DOIUrl":"10.1530/REP-24-0184","url":null,"abstract":"<p><strong>In brief: </strong>Ovulation, the female reproductive process whereby fertilizable oocytes are released from a mature ovarian follicle, is widely seen in all animals that sexually reproduce. This paper reveals that, despite the remarkably diverse styles of ovulation among animal taxa, most ovulate via follicle rupture and suggests that the rupture process may operate via similar cellular mechanisms across animals.</p><p><strong>Abstract: </strong>Ovulation is the process by which a fertilizable oocyte is extruded from the interior of the follicle. Herein, we conducted a literature survey to explore the ovulation patterns of 11 sexually reproducing species belonging to 10 animal phyla. These results indicate a large variety of ovulation patterns. Further comparative biological and evolutionary considerations of these results led us to conclude that most female animals ovulate via follicle rupture. We propose that in all animals that ovulate by follicle rupture, two cellular events may be critically involved in the process: i) the disintegration of cell junctional systems leading to intracellular cytoskeleton rearrangement in the follicle cells and ii) the degradation of extracellular matrix (ECM) proteins filled between follicle cells. These events may result in follicular cell deformation and increased motility, both of which are necessary for the formation of a path through which an oocyte escapes from the follicle. In addition to the requirement of ECM degradation for disintegrating cell junctions, intensive ECM protein degradation at the apical region of the follicle probably became increasingly important in late-evolving animals, such as vertebrates, in which a thick follicle wall containing a large abundance of ECM proteins is formed. We also considered hypothetical scenarios for the evolution of ovulation in these animals. Furthermore, this article discusses future problems that need to be solved for a more comprehensive understanding of ovulation in the animal kingdom.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early ovarian differentiation in the tammar wallaby and the effects of exposure to bisphenol A.","authors":"Mario T Peiris, Yu Chen, Geoff Shaw, Marilyn B Renfree","doi":"10.1530/REP-24-0259","DOIUrl":"10.1530/REP-24-0259","url":null,"abstract":"<p><strong>In brief: </strong>Ovarian differentiation in tammar wallabies begins after birth, allowing direct experimental manipulation during the period of differentiation. Using this unique model, we demonstrate that the environmental endocrine-disrupting chemical bisphenol A (BPA) interferes with normal morphological development and gene expression in the developing ovary.</p><p><strong>Abstract: </strong>BPA, an environmental endocrine disruptor, is used widely in the manufacturing of various plastics. While BPA can have detrimental effects on fertility and reproductive health, the effects of BPA on early ovarian differentiation in mammals remain unclear. Marsupials have undifferentiated gonads at birth, so this study investigated the gross morphology, protein localisation of FOXL2 and FST and the expression profile of key ovarian differentiating genes FOXL2, WNT4, FST, ESR1 and ESR2 every 2 days from the day of birth to day 10 postpartum (pp) in the marsupial tammar wallaby. A second group of newborn female pouch young were treated with 50 μg/kg of BPA daily from day 0 to day 10 pp, and the morphology and gene expression were examined at day 10 pp. Ovigerous cords in tammar ovaries were first formed between day 2 and day 4 pp. FOXL2 localisation became nuclear by day 4 in pre-granulosa cells. FST was initially in the cytoplasm of pre-granulosa cells at day 2 pp but was then secreted into the extracellular matrix in ovaries by day 10 pp. FOXL2, FST, ESR1 and ESR2 mRNA were upregulated in ovaries around day 2-4 pp, indicating that ovarian differentiation in the tammar begins from day 2 to day 4 pp. Interestingly, BPA treatment from day 0 to day 10 pp blocked the morphological differentiation of the cortex and medulla and ovigerous cord formation and downregulated the expression of FST and FOXL2 at day 10 pp.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased miR-486-5p is involved in lipopolysaccharide-induced HTR-8/SVneo cell dysfunction by promoting SMAD2 expression.","authors":"Yan Gu, Ling-Han Chen, Long Yang, Yan Shi, Hao-Lan Xu, Ya-Wei Xin, Ning Song, Wen-Wen Gu, Jian Wang","doi":"10.1530/REP-23-0502","DOIUrl":"10.1530/REP-23-0502","url":null,"abstract":"<p><strong>In brief: </strong>Insufficiency of extravillous trophoblast (EVT) cell invasion is implicated in pregnancy complications. This study reveals the roles of the miR-486-5p/Smad2 pathway in lipopolysaccharide (LPS)-induced EVT dysfunctions and in the pathogenesis of early pregnancy loss (EPL).</p><p><strong>Abstract: </strong>Placenta-associated pathologies, including EPL and preeclampsia, are characterized by insufficient EVT invasion. Previously, downregulated miR-486-5p expression was shown to inhibit the invasion of EVTs, and decreased peripheral miR-486-5p expression was associated with EPL. However, the exact roles of miR-486-5p in the pathogenesis of EPL, as well as the molecular pathway underlying the role of miR-486-5p in EVT invasion, remain poorly understood. In this study, decreased miR-486-5p expression in the uterine embryo implantation site on gestational day 8.5 and increased uterine expression of Smad2, a target of miR-486-5p, were observed in an LPS-induced EPL model. The invasion and viability of the immortalized human EVT line, HTR-8/SVneo, were inhibited by LPS, accompanied by reduced miR-486-5p expression. LPS promoted Smad2 expression, which was attenuated by the miR-486-5p mimics. The downregulation of Smad2 effectively restored the impaired invasion and viability of HTR-8/SVneo cells caused by LPS or the miR-486-5p inhibitor. Furthermore, LPS promoted TNFα production in HTR-8/SVneo cells, whereas both siSMAD2 and miR-486-5p mimics reversed this effect. An analysis of human decidua single-cell RNA sequencing and transcriptome datasets derived from Gene Expression Omnibus revealed that, compared with that in control early pregnant women, SMAD2 expression was significantly increased in recurrent miscarriage patients. Collectively, these data suggest that decreased miR-486-5p expression might lead to EPL, at least partially by inhibiting invasion and/or promoting TNFα production in EVTs by targeting SMAD2.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"REPRODUCTIVE HEALTH IN TRANS AND GENDER DIVERSE PATIENTS: Fertility treatment and preservation options for transgender and gender diverse people.","authors":"Elizabeth Rubin, Marissa Palmor, Paula Amato","doi":"10.1530/REP-24-0120","DOIUrl":"10.1530/REP-24-0120","url":null,"abstract":"<p><strong>In brief: </strong>Many transgender and gender diverse (TGD) people want to have biologically related children. This review summarizes and discusses the options for fertility treatment and preservation in TGD adults and adolescents, with an emphasis on gender-affirming hormone therapy in the context of fertility treatment, clinical management strategies to minimize gender dysphoria during treatment and major factors in future use of cryopreserved gametes.</p><p><strong>Abstract: </strong>Years of growing research demonstrate that TGD people desire fertility counseling and family building; however, social and medical factors can impact future fertility options. Fortunately, TGD individuals have many viable options for family building using their own gametes and/or reproductive organs. However, the nuanced ways in which different gender-affirming treatments affect reproduction, the interplay with nontreatment-related infertility factors and mitigation of likely dysphoria triggers are all critical to actual utilization. This review focuses on fertility treatment and preservation options for TGD patients and highlights these influential social and medical factors. Fertility treatments may be associated with worsening gender dysphoria in TGD people, and an affirming clinical environment and conscientious provider approach is paramount to treatment success. However, reducing gender dysphoria can also require specific changes to medically assisted reproduction and sperm collection protocols, some of which carry the potential for diminished outcomes or unknown effects. Adolescents undergoing fertility preservation treatments may need more support or additional protocol modifications, and outcomes may be poorer in this age group compared with adults. Testicular and ovarian tissue cryopreservation may present a fertility preservation option for prepubertal TGD children; however, in vitro gamete maturation remains experimental in this situation.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide profiling of the epigenetic landscape of histone variant TH2B in murine oocytes and pre-implantation embryos.","authors":"Isha Singh, Priyanka Parte","doi":"10.1530/REP-24-0035","DOIUrl":"10.1530/REP-24-0035","url":null,"abstract":"<p><strong>In brief: </strong>This study investigates the role of TH2B in pre-implantation embryos and found that TH2B deposition varies between gametes but rapidly redistributes in two-cell embryos after fertilization. Our ultra-low-input native chromatin immunoprecipitation and sequencing (ULI-NChIP-seq) revealed that TH2B is enriched in early chromatin but decreases after the two-cell stage, with strong correlations to key regulatory regions, histone modifications and transposable elements (TEs), indicating its critical role in zygotic genome activation and early developmental processes.</p><p><strong>Abstract: </strong>The histone variant TH2B, enriched in oocytes, sperm and early embryos, decreases as embryos differentiate into pre-gastrula stages. Despite its presence, the role of TH2B in epigenetic reprogramming during early embryonic development remains largely under-researched. Our study employed ULI-NChIP-seq to analyze the genome-wide distribution of TH2B in metaphase II (MII) oocytes and early embryos. We found that TH2B is enriched in the chromatin of oocytes and two-cell stage embryos but becomes less prevalent after the two-cell stage. Correlation analysis revealed that the TH2B chromatin patterns in sperm and pre-implantation embryos are more similar to each other than to those in MII oocytes. Gene ontology (GO) analysis of TH2B-occupied loci linked them to various developmental processes including oogenesis, fertilization, chromatin modification and transcription regulation. The study also identified a strong association of TH2B with specific TEs, particularly long terminal repeats, which are known to regulate pre-implantation development. Additionally, early embryos showed H3K9me3 marks at TH2B-bound loci. TH2B exhibited strong correlations with H2A.Z and H3.3 in the two-cell and eight-cell stages, a positive association with H3K27Ac and H3K4me3 and a negative correlation with H3K27me3. Allelic reprogramming analysis of TH2B in embryos from C57BL/6J and DBA/2J crosses revealed differential dynamics between maternal and paternal alleles, with a notable paternal bias at the promoter in two-cell embryos. Thus, TH2B's enrichment in early embryonic stages and its association with key regulatory regions and histone modifications underscore its importance in zygotic genome activation and subsequent developmental processes.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain-derived neurotrophic factor stimulates hypothalamic and gonadal reproductive hormones and oocyte maturation in zebrafish.","authors":"Chinelo Uju, Katayoon Karimzadeh, Suraj Unniappan","doi":"10.1530/REP-24-0233","DOIUrl":"10.1530/REP-24-0233","url":null,"abstract":"<p><strong>In brief: </strong>The brain-derived neurotrophic factor (BDNF) has been shown to regulate metabolism in zebrafish. This research shows that Bdnf is a regulator of female zebrafish reproduction and reproductive hormones.</p><p><strong>Abstract: </strong>BDNF is a peptide widely known for its role in neurogenesis and synaptic plasticity. Its expression in non-neuronal tissues has been reported. In mammals, it is involved in ovarian development, follicle growth, oocyte maturation and early embryonic development. In zebrafish, it was demonstrated that Bdnf increases food intake and regulates metabolism. Reproduction and metabolism are tightly linked. We hypothesized that Bdnf modulates reproductive hormones and reproductive functions in zebrafish. This study aimed to determine Bdnf expression in the zebrafish reproductive axis and whether it modulates the reproductive endocrine milieu and oocyte biology in zebrafish. Our results show that bdnf and its receptor trkb and Bdnf-like immunoreactivity are present in zebrafish gonads and liver cells. This suggests Bdnf local production and possible actions within the gonads and liver. Intraperitoneal administration of 1, 10 or 100 ng/g body weight BDNF significantly (ANOVA, P < 0.05) increased sgnrh/cgnrh-II, kiss1 and cyp19a1b mRNAs in the zebrafish brain, steroidogenic enzymes (star and cyp19a1a) and key receptors in the zebrafish gonads. In vitro incubation of zebrafish liver cells with BDNF significantly (ANOVA, P < 0.05) increased estrogen receptor mRNAs and vitellogenin concentrations (ELISA) in the cells. BDNF (100 ng/mL) induced (ANOVA, P < 0.05) oocyte maturation in vitro at 24 h post-incubation and significantly upregulated cumulus-expansion-related genes (ANOVA, P < 0.05). Overall, our findings indicate a stimulatory role for Bdnf in the reproductive axis of zebrafish. This provides impetus for future research on its mechanism of action and potential practical applications to enhance reproduction in aquaculture.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"REPRODUCTIVE HEALTH IN TRANS AND GENDER DIVERSE PATIENTS: Contraception considerations in transmasculine and gender diverse adolescents and young adults.","authors":"Kirsten Das, Veronica Gomez Lobo","doi":"10.1530/REP-24-0080","DOIUrl":"10.1530/REP-24-0080","url":null,"abstract":"<p><strong>In brief: </strong>Transmasculine and gender diverse adolescents and young adults can often have nuanced considerations when utilizing contraception. This narrative review discusses contraception utilization patterns and specific considerations in this population and proposes a patient-oriented comparison of contraceptive options.</p><p><strong>Abstract: </strong>Contraception care is an important aspect of comprehensive gender-affirming care in transgender and gender diverse (TGD) adolescents and young adults (AYAs). TGD AYAs seek contraception care for a variety of reasons, and several important considerations are unique to this population. In addition to pregnancy prevention, transmasculine and gender nonbinary persons may seek contraception to achieve amenorrhea and reduce gender dysphoria, or as part of their gender-affirming journey. While patients on testosterone therapy often experience amenorrhea, pregnancy has been reported and testosterone is not a form of contraception. Visits for contraceptive counseling provide an opportunity to discuss fertility goals and preservation planning as well as the possibility that some methods may provide endometrial protection. In this narrative review, we analyze the current literature and discuss specific considerations for contraceptive use in this population. We also propose a contraception overview for shared decision making for patients and their clinicians.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IMPACT OF REAL-LIFE ENVIRONMENTAL EXPOSURES ON REPRODUCTION: Phthalate exposure and reproductive effects in rodents: a model for approaches on the protective role of natural products.","authors":"Wellerson Rodrigo Scarano, Marina Trevizan Guerra, Juliana Elaine Perobelli, Glaura S A Fernandes, Arielle Cristina Arena, Ariana Musa de Aquino, Vanessa Aguiar Rocha, Natalia Magosso, Patrick Vieira Souza, Luis Fernando Barbisan","doi":"10.1530/REP-24-0186","DOIUrl":"10.1530/REP-24-0186","url":null,"abstract":"<p><strong>In brief: </strong>Exposure to phthalates, alone or in mixtures, at different periods of development alters the reproductive function of males and females, especially in rodents, where they have been most studied. This review addressed the most recent data (last 10 years) on exposure to phthalates in different scenarios and how the use of natural products could mitigate the harmful effects caused by exposure at different stages of development.</p><p><strong>Abstract: </strong>This review article summarizes the experimental findings in rodents published between 2014 and 2024 concerning phthalates exposure and reproductive outcomes. Rodents were chosen for this review because most studies that have focused on developmental aspects in different phases of exposure and that address more in-depth reproductive mechanisms have been carried out in mice and rats. The evidence of adverse effects of phthalates on fetal development and human and animal reproduction is extensive, with impacts ranging from gene expression to physiological alterations. Despite the large volume of scientific papers pointing out the harmful effects of exposure to phthalates, isolated or in mixtures, at different developmental periods, most of them are associated with the maternal exposure and long-term effects in the offspring. Regular vegetables, fruits, fish, dairy products, and whole grains intake rich in bioactive compounds can mitigate the adverse effects of endocrine-disrupting chemicals in humans and animals at different developmental periods. Various food bioactive compounds (FBCs), such as genistein, resveratrol, lycopene, vitamin E, curcumin, selenium, and plant secondary metabolites (PSMs), present antioxidant, anti-inflammatory, antitumor, and other biological properties with the potential to reduce deleterious effects of phthalates on the reproductive tract. In this review, we aimed to summarize the main studies carried out in the last decade about phthalate exposure and reproductive disorders in males and females (at different developmental critical windows). In addition, we proposed some FBCs and PSMs that could attenuate the main adverse effects caused by phthalate exposure on male reproduction because there is a lack of studies with females.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant FSH induced progesterone via partially regulating let-7 expression in human and mouse granulosa cells.","authors":"Jing Chen, Lin Chen, Weimin Liu","doi":"10.1530/REP-24-0074","DOIUrl":"https://doi.org/10.1530/REP-24-0074","url":null,"abstract":"<p><p>Serum progesterone may increase prior to ovulation trigger in in vitro fertilization patients, jeopardizing endometrial receptivity and therefore live birth rate. Recombinant FSH (rFSH) promotes progesterone production from human granulosa cells. Yet, the role of FSH on progesterone production need deeper exploration. Studies were conducted in human primary cumulus cells from IVF cycles, human granulosa cell line and mice primary granulosa cells. The relative expression of let-7 was evaluated using real time PCR. Human primary cumulus cells were collected from individual cumulus-oocyte complex of high-progesterone patients (serum progesterone level higher than 5 nM, n=18) and control group (serum progesterone level less than 5 nM, n=25). The expression of let-7a in human primary cumulus cells was markedly reduced in the high-progesterone group compared to the control. The serum progesterone level was augmented after rFSH treatment at dose of 0.5, 1 and 2.5 IU along with reduce expression of let-7a. Progesterone level in cultured medium from isolated mouse primary granulosa cells and human granulosa cell line were significantly elevated with rFSH at 12.5, 25, 50 IU/L concentrations with decreased expression of let-7a. Besides, there was a robustly increase of let-7a expression in let-7a mimics-transfected group and decrease in let-7a inhibitor-group with or without rFSH treatment and the opposite trend of progesterone. Collectively, our findings revealed the key role of let-7 in rFSH induced progesterone level both in human and mouse granulosa cells, providing potential mechanism for premature progesterone rise.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}