Reproduction最新文献

{"title":"Irisin decreases follicle development in cattle and inhibits theca cell steroidogenesis through focal adhesion kinase signaling.","authors":"Mathilde Daudon, Christelle Ramé, Marcos H Barreta, Alfredo Q Antoniazzi, Valério M Portela, Europa Meza-Serrano, Joëlle Dupont, Christopher A Price","doi":"10.1530/REP-24-0352","DOIUrl":"10.1530/REP-24-0352","url":null,"abstract":"<p><strong>In brief: </strong>Irisin is a muscle and adipose-derived hormone that is secreted in response to negative energy balance in cattle. We show here that irisin reduced follicle growth and theca cell function.</p><p><strong>Abstract: </strong>At the onset of lactation, dairy cattle are anestrous owing mainly to a state of negative energy balance. Adipose tissue is mobilized to meet the energy demands of milk production, and this alters the secretion of adipose-derived hormones, called adipokines. Irisin is a myokine/adipokine that may play a role in fertility; plasma concentrations increase in cattle postpartum, and irisin decreased progesterone and estradiol secretion from bovine granulosa cells in vitro. To our knowledge, the effects of irisin on bovine theca cell function in vitro and on follicle growth in vivo have not been reported. We hypothesized that irisin negatively affects theca cell function in vitro and causes follicle regression in vivo using well-established bovine models. Under physiological concentrations of insulin (0.2 ng/mL), irisin did not affect glucose uptake, but decreased testosterone secretion and stimulated PTK2 and MTOR phosphorylation. Inhibiting PTK2 activity abolished the ability of irisin to decrease testosterone secretion. Injection of irisin directly into a growing follicle in vivo caused follicle regression. We conclude that irisin decreases bovine theca cell steroidogenesis through PTK2 signaling, and combined effects on theca and granulosa cells cause follicle regression.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586437","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":"Uterine stromal but not epithelial PTGS2 is critical for murine pregnancy success.","authors":"Noura Massri, Ripla Arora","doi":"10.1530/REP-24-0408","DOIUrl":"10.1530/REP-24-0408","url":null,"abstract":"<p><p>The use of non-steroidal anti-inflammatory drugs that target prostaglandin synthase (PTGS) enzymes has been implicated in miscarriage. Further, PTGS2-derived prostaglandins are reduced in the endometrium of patients with a history of implantation failure. However, in the mouse model of pregnancy, peri-implantation PTGS2 function is controversial. Some studies suggest that Ptgs2 -/- mice display deficits in ovulation, fertilization and implantation, while other studies suggest a role for PTGS2 only in ovulation but not implantation. Further, the uterine cell type responsible for PTGS2 function and the role of PTGS2 in regulating implantation chamber formation are not known. To address this, we generated tissue-specific deletion models of Ptgs2. We observed that PTGS2 ablation from the epithelium alone in Ltf cre/+ ; Ptgs2 f/f mice and in both the epithelium and endothelium of the Pax2 cre/+ ; Ptgs2 f/f mice does not affect embryo implantation. Further, deletion of PTGS2 in the ovary, oviduct and uterus using Pgr cre/+ ; Ptgs2 f/f does not disrupt pre-implantation events but instead interferes with post-implantation chamber formation, vascular remodeling and decidualization. While all embryos initiate chamber formation, more than half of the embryos fail to transition from blastocyst to epiblast stage, resulting in embryo death and resorbing decidual sites at mid-gestation. Thus, our results suggest no role for uterine epithelial PTGS2 in early pregnancy but instead highlight a role for uterine stromal PTGS2 in modulating post-implantation embryo and implantation chamber growth. Overall, our study provides clarity on the compartment-specific role of PTGS2 and provides a valuable model for further investigating the role of stromal PTGS2 in post-implantation embryo development.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nicotinamide riboside supplementation protects against maternally diabetes-associated decline in oocyte quality.","authors":"Chenlu Wei, Xinxin Zeng, Keer Wang, Mengchen Wang, Min Lei, Zhenye Zhu, Yining Xu, Yanqing Zhao, Qingling Yang, Ying-Pu Sun","doi":"10.1530/REP-24-0350","DOIUrl":"10.1530/REP-24-0350","url":null,"abstract":"<p><p>Diabetes mellitus is strongly correlated with a decline in oocyte quality, however, non-invasive and effective methods to improve this issue have yet to be fully development. Here, we demonstrate that in vivo supplementation with nicotinamide riboside (NR) 400 mg/kg/day for 14 days effectively enhances the quality of oocytes from diabetic mice induced by streptozocin 190 mg/kg by restoring nicotinamide adenine dinucleotide (NAD+) levels. NR supplementation not only improved superovulation function of diabetic mice but also improved their oocyte quality and embryonic development potential after fertilization by maintaining normal spindle structure and alleviating mitochondrial dysfunction. In addition, NR supplementation reduced ROS levels in oocytes rom diabetic mice. Overall, our findings suggest that dietary NR supplementation is a viable strategy to protect oocytes from diabetes-related deterioration, thereby enhancing reproductive outcomes in maternal diabetes and improving the efficacy of assisted reproductive technology.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664395","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":"Single nucleotide polymorphism at 5' UTR of H2BC1 and promoter methylation influence TSH2B expression.","authors":"Aniket Patankar, Kairavi Joshi, Digumarthi V S Sudhakar, Rahul Gajbhiye, Suchitra Surve, Priyanka Parte","doi":"10.1530/REP-24-0382","DOIUrl":"https://doi.org/10.1530/REP-24-0382","url":null,"abstract":"<p><p>The transition from histones to protamines during spermiogenesis plays a crucial role in shaping the male epigenome, and any changes in this process can impact fertilization potential and the ability of sperm to support early embryogenesis. In our previous research, we observed reduced levels of TSH2B in the sperm of infertile men with oligozoospermia and oligoasthenozoospermia. However, the regulatory mechanisms of the H2BC1 gene, which encodes TSH2B, in the testes are not yet understood. In this study, we investigated whether H2BC1 expression is influenced by single nucleotide polymorphisms (SNPs) in the 5' untranslated region (5' UTR) and promoter methylation. Luciferase assays were performed to assess the impact of 5' UTR variants in vitro and pyrosequencing was done to evaluate promoter methylation of the H2BC1 gene in sperm of fertile and infertile men. Our findings suggest that the 5' UTR variants rs4711096 (c.-83A>G) and rs4712959 (c.-80 C>T) positively regulate H2BC1 expression. Methylation analysis indicates hypermethylation of CpG sites particularly at CpGs 2, 3, and 9 in H2BC1 can influence H2BC1 expression. This study offers new insights into the regulation of testis-specific genes.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731350","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":"Meiotic arrest, resumption, and TZP retraction in bovine COCs undergoing pre-IVM: lessons from a refined GV stage classification.","authors":"Helena Fabiana Reis de Almeida Saraiva, Juliano Rodrigues Sangalli, Luana Alves, Juliano Coelho da Silveira, Flávio Vieira Meirelles, Felipe Perecin","doi":"10.1530/REP-23-0235","DOIUrl":"10.1530/REP-23-0235","url":null,"abstract":"<p><p>The nuclear, cytoplasmic, and molecular maturation of the mammalian oocyte is a finely orchestrated sequence of events that relies on proper cumulus-oocyte communication. Bovine oocytes enter the in vitro maturation systems at the germinal vesicle stage (GV) exhibiting four different chromatin configurations (GV0-GV3). Herein, we associate the oocyte chromatin and nuclear lamina configurations to propose a refined GV classification (GV0, GV1.1-GV1.3, GV2.1-GV2.3, and GV3.1-GV3.3). This refined GV classification system was correlated with oocyte meiosis resumption and transzonal projections (TZPs) density of COCs submitted to three IVM systems (control IVM; and a modified IVM preceded or not by a pre-IVM step). Pre-IVM resulted in lower polar body extrusion rates at 19 h IVM, albeit ~24% of the oocytes extruded their first polar body at 9 h IVM. Pre-IVM sustained 80% of oocytes meiotically arrested but altered GV distribution, reducing GV2 and increasing GV1.3 and GV3.3 categories. Pre-IVM reduced TZP densities predominantly in pre-matured GV3 and GVBD COCs. At 9 h of IVM, both groups matured in modified IVM showed lower TZP densities compared to immature and IVM control. Gene expression supports the TZP density differences, with ERK2 and PRKACA upregulation in pre-matured cumulus and in modified IVM groups at 9 h of IVM. GDF9 and BMP15 levels were similar between treated and control groups at all time points. Our findings indicate that despite the IVM system, the initial oocyte GV stage influences pre-IVM and IVM outcomes. The refined GV classification system is a useful tool to oocyte biologists.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731340","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":"Increased plugging latency in cycling epiERα -/- (Esr1 f/- Wnt7a Cre/+ ) mice.","authors":"Jonathan Matthew Hancock, Taylor Elijah Martin, Zidao Wang, Jackson Kyle Sundgren, Xiaoqin Ye","doi":"10.1530/REP-24-0447","DOIUrl":"10.1530/REP-24-0447","url":null,"abstract":"<p><p>Wnt7a-Cre is a commonly used driver for generating uterine epithelial conditional knockout mice, such as epiERα -/- (Esr1 f/- Wnt7a Cre/+ ) and epiPR -/- (Pgr f/- Wnt7a Cre/+ ). We noticed that epiERα -/- females, but not epiPR -/- females, have prolonged plugging latency, which is the duration between continuous cohabitation and detection of the first vaginal plug (a sign of mating). Mating occurs in proestrus and/or estrus stages of the estrous cycle. Vaginal cytology detected estrous cyclicity in all mice examined, although epiERα -/- mice had leukocyte-dominant vaginal cytology throughout the estrous cycle and their estrous cyclicity appeared less regular. Estrous cyclicity and mating activity are regulated by the hypothalamic-pituitary-ovarian axis, in which kisspeptin plays essential roles. ERα and PR are expressed in the rostral periventricular area of the ventricle (RP3V) and arcuate nucleus (ARC) kisspeptin neurons in the hypothalamus. It has been reported that Esr1 f/f Kiss1-Cre mice lack estrous cyclicity, while Pgr f/f Kiss1-Cre mice have normal estrous cyclicity at two months old, and Wnt7a is highly expressed in ARC. The prolonged plugging latency in epiERα -/- mice could be contributed by the deletion of ERα in Wnt7a-positive cells in ARC. Wnt7a-Cre was also used to generate uterine epithelial RhoA-deficient mice, epiRhoA -/- (RhoA f/- Wnt7a Cre/+ ). However, both female and male RhoA f/- Wnt7a Cre/+ mice had hydrocephalus and died within a few weeks of age. Our observations of increased plugging latency in epiERα -/- mice and hydrocephalus in RhoA f/- Wnt7a Cre/+ mice exemplify unintended neuronal gene deletion using Wnt7a-Cre for uterine epithelial-specific gene deletion.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11859491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD40 ligand and CD40: expression, regulation and function at the maternal-conceptus interface in pigs.","authors":"Inkyu Yoo, Soohyung Lee, Yugyeong Cheon, Tae Sub Park, Hakhyun Ka","doi":"10.1530/REP-24-0396","DOIUrl":"10.1530/REP-24-0396","url":null,"abstract":"<p><strong>In brief: </strong>The CD40 ligand-CD40 signaling system expressed at the maternal-conceptus interface in pigs is involved in regulating maternal immunity by modifying endometrial endothelial cell function during early pregnancy. This paper reveals the role of CD40 ligand-CD40 signaling at the maternal-conceptus interface in pigs.</p><p><strong>Abstract: </strong>To successfully establish and maintain pregnancy in pigs, a variety of factors must work together at the maternal-conceptus interface to form an immune environment appropriate for both the mother and the conceptus. Our transcriptomics study has shown that cluster of differentiation ligand 40 (CD40L) and its receptor CD40, which are known to play important roles in regulating cell- and antibody-mediated immunity, are expressed in the endometrium during early pregnancy. However, the roles of the CD40L and CD40 signaling system are not well understood. Therefore, we determined the expression, regulation and function of CD40L and CD40 at the maternal-conceptus interface in pigs. The endometrium expressed CD40L and CD40 mRNAs at the greatest levels on day 15 of pregnancy. The CD40L protein was localized predominantly to luminal epithelial cells on day 15 of pregnancy, and the CD40 protein was found in luminal epithelial, stromal and vascular endothelial cells in the endometrium during pregnancy. During early pregnancy, the conceptus expressed CD40 but not CD40L and chorioallantoic tissues during mid- to late pregnancy expressed both CD40L and CD40. Interferon-γ increased the expression of CD40L and CD40 in endometrial explants. CD40L increased the migration but not the proliferation of cultured porcine uterine endothelial (pENDO) cells in vitro. In addition, CD40L affected the expression of genes related to angiogenesis, cell adhesion, chemokines and immunity in pENDO cells. These results suggest that the CD40L-CD40 system might play an important role in the establishment of pregnancy in pigs by regulating endometrial endothelial cell function during the implantation period.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060457","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":"Loss of PRICKLE1 leads to subfertility, aberrant extracellular matrix and abnormal myometrial architecture in mice.","authors":"Emily R Roberts, Sornakala Ganeshkumar, Sumedha Gunewardena, Vargheese Chennathukuzhi","doi":"10.1530/REP-24-0344","DOIUrl":"10.1530/REP-24-0344","url":null,"abstract":"<p><strong>In brief: </strong>PRICKLE1, a WNT/planar cell polarity (PCP) protein that is downregulated in uterine leiomyoma, plays an important role in myometrial tissue architecture and extracellular matrix (ECM) deposition. This paper shows that myometrial-specific ablation of the mouse Prickle1 gene results in a uterine leiomyoma phenotype.</p><p><strong>Abstract: </strong>Uterine leiomyomas (ULs) are the most prevalent benign tumors of the female reproductive tract, originating from the myometrium and affecting over 75% of reproductive-age women. Symptoms of UL include pelvic pain, pressure, dysmenorrhea, menorrhagia, anemia and reproductive dysfunction. Currently, there is no effective long-term pharmacotherapy for UL, making them the leading cause of hysterectomies in the United States. The lack of treatment options is attributed to the absence of accurate animal models and a limited understanding of UL pathogenesis. Previous research has shown that the loss of repressor of element 1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) within the myometrium promotes UL pathogenesis. In addition, deletion of Rest in the mouse myometrium leads to a UL phenotype. PRICKLE1, also known as Rest-interacting LIM-domain protein (RILP), is required for nuclear localization of REST and Wnt/PCP signaling, making it a critical target for UL studies. In the context of PCP, smooth muscle cells in UL show abnormal organization, aberrant ECM structure and expression levels, potentially influenced by PRICKLE1 loss. The exact role of PRICKLE1 and Wnt/PCP in UL pathogenesis remains unclear. To explore PRICKLE1's role in UL, we deleted Prickle1 using our myometrial-specific iCre. Our findings demonstrate that Prickle1 loss in the myometrium results in a UL phenotype characterized by altered collagen expression, excessive ECM deposition, aberrant smooth muscle cell organization, increased Esr1 and Pgr expression and dysregulated Wnt/PCP signaling. This novel mouse model serves as a valuable preclinical tool for understanding UL pathogenesis and developing future pharmacotherapies.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Special series on reproductive health in transgender and gender-diverse patients.","authors":"Molly B Moravek, Gene de Haan, Vasantha Padmanabhan","doi":"10.1530/REP-24-0455","DOIUrl":"10.1530/REP-24-0455","url":null,"abstract":"","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787022","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":"Hypoxia-inducible factor inhibition affects luteal function with no effect on fertility in mice.","authors":"Rocío Celeste Marinoni, María José España De Marco, Candela Velazquez, Katherine Prost, Fernanda Parborell, Marta Tesone, Dalhia Abramovich","doi":"10.1530/REP-24-0313","DOIUrl":"10.1530/REP-24-0313","url":null,"abstract":"<p><strong>In brief: </strong>Formation and function of the corpus luteum strongly rely on active angiogenesis. This study demonstrates the role of the hypoxia-inducible factor (HIF) in luteinization with no effect on fertility.</p><p><strong>Abstract: </strong>HIFs are transcription factors responsible for sensing low oxygen levels and, in response, inducing the transcription of numerous genes. One of the main processes stimulated by HIFs is the formation of new vessels to increase oxygen supply to the tissue. Formation of the corpus luteum strongly depends on the vasculature, and active angiogenesis occurs during luteinization. In this study, we aimed to analyze the role of HIF in the early formation of corpus luteum and its function, and in female fertility. To this aim, we superovulated mice using equine chorionic gonadotropin and human chorionic gonadotropin (hCG) and administered the HIF inhibitor acriflavine (ACF) to the mice 3 h before hCG. We found a decrease in ovarian HIF1A and VEGFA and in the vascular area in the animals treated with ACF. Moreover, we observed an increase in aberrant structures in the ovaries and in luteal cell apoptosis. Serum progesterone levels were decreased together with ovarian STAR expression. However, the animals treated with ACF during the early formation of the corpus luteum were completely fertile and no alterations were observed when the treated females were mated with fertile males. These results collectively suggest that HIF regulates gonadotropin-induced corpus luteum formation by acting on luteal blood vessel formation, luteal cell survival and progesterone synthesis. However, adequate HIF activity may not be essential to achieve and maintain pregnancy. These findings are significant to better understand the complex mechanisms of corpus luteum formation and identify potential abnormalities to allow better knowledge of ovarian physiology and pathologies in which this factor could be involved.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802207","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}