Reproduction最新文献

{"title":"Comparison of three modified mouse models of adenomyosis based on invagination theory.","authors":"Song Guo, Di Zhang, Yilin Guo, Hao Wang, Jinxia Zhou, Yuewen Zhao, Li Yan, Fang Lian","doi":"10.1530/REP-25-0158","DOIUrl":"10.1530/REP-25-0158","url":null,"abstract":"<p><strong>In brief: </strong>There is no ideal animal model of adenomyosis, which reflects the imperfect understanding of complex human pathogenesis. In this study, we successfully induced adenomyosis in a mouse model via sharp-blunt trauma, which more closely mimics clinical observations in humans than previous models.</p><p><strong>Abstract: </strong>Adenomyosis is a common gynecological disease in women of reproductive. To date, a satisfactory animal model of adenomyosis has not been established. In this study, 51 female mice were divided into four groups: negative control, an abdominal skin incision was made and sutured without uterine injury; puncture, the uterine horn was punctured using a needle; dilation & curettage, a self-made curette was used to simulate D&C; puncture + dilation & curettage, the uterine horn was punctured, and dilation & curettage were performed. The mice were euthanized 2 weeks, 1 month, or 2 months post-surgery, and the uteruses were harvested. Validity was assessed by histopathological examination. The levels of EMT markers were also detected among the groups. The success rate of adenomyosis induction was higher in the Punct + D&C group than in other groups at all three time points. The highest success rate was observed in the Punct + D&C group 2 months post-surgery. Significantly increased VIM expression was observed in ectopic lesions compared with eutopic endometrium in the Punct + D&C group 2 weeks post-surgery. In addition, VIM expression in eutopic endometrium in the Punct + D&C group was significantly higher than that in the sham group 2 months post-surgery. CDH1 expression was downregulated in the Punct + D&C group compared with the sham group at 2 weeks and 2 months post-surgery. In this study, we successfully established a mouse model of adenomyosis based on invagination theory, which is low cost, quick to establish, and does not interfere with hormone secretion.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576205","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":"Gene expression pattern predictive of human ovarian follicle development and maturation.","authors":"Samantha Sperduti, Lara Baschieri, Danilo Cimadomo, Clara Lazzaretti, Federica Davolio, Federica Innocenti, Marilena Taggi, Laura Albricci, Laura Rienzi, Alberto Vaiarelli, Filippo Maria Ubaldi, Manuela Simoni, Livio Casarini","doi":"10.1530/REP-25-0176","DOIUrl":"10.1530/REP-25-0176","url":null,"abstract":"<p><strong>In brief: </strong>Granulosa cells from small antral follicles (SFs; diameter <10 mm), collected at the end of controlled ovarian cycles, differ from large ovarian follicles (LFs; >16 mm) for their molecular signatures. SFs retain characteristic of early antral follicles and the ratio between follicle-stimulating hormone receptor (FSHR) and G protein-coupled receptor (GPER) discriminates between mature and immature-like follicles.</p><p><strong>Abstract: </strong>Ovarian follicle maturation is regulated by a network of genes involved in cell growth, differentiation, oocyte selection, and steroidogenesis. In this study, we compared the expression of developmental markers and intrafollicular steroid levels in granulosa cells from small (SFs; diameter <10 mm) vs large human ovarian follicles (LFs; >16 mm). Since samples were collected from both conventional ovarian stimulation cycles and the second phase of DuoStim protocol, differences between follicles of follicular and luteal origin were also evaluated. Although both SFs and LFs displayed periovulatory markers, such as LHCGR gene expression, SFs exhibited relatively high expression levels of early antral markers, i.e., FSHR, GPER, AMHR2, CCND2 and CYP19A1 genes. This was different in LFs, which have overall homogeneous gene expression pattern. Gene expression data reflect the capability to convert androgens to estrogens, which is higher in SFs than LFs. These differences did not change when follicles from conventional and the second stimulation of DuoStim protocol were compared, confirming previous clinical observations that suggested similar quality and outcomes from oocytes collected in different follicular waves. In conclusion, SFs and LFs exhibit distinct characteristics, including specific size, gene expression patterns, and steroidogenic capabilities, regardless of their follicular or luteal origin. According to previous reports, the FSHR/GPER ratio could discriminate between mature and immature-like follicles collected at the end of controlled ovarian cycles, and between two sub-populations of LFs.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637892","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":"Acetaminophen overdose suppresses human extravillous trophoblast invasion by downregulating SP1-mediated MMP2 expression.","authors":"Yuanyuan Jia, Siwei Luo, Beibei Bi, Xiaoyu Han, Jung-Chien Cheng, Lanlan Fang","doi":"10.1530/REP-25-0185","DOIUrl":"https://doi.org/10.1530/REP-25-0185","url":null,"abstract":"<p><strong>In brief statement: </strong>Acetaminophen (APAP) overdose impairs extravillous trophoblast (EVT) cell invasion by inhibiting AKT signaling, leading to downregulation of SP1 and reduced MMP2 expression. These findings highlight a potential mechanism by which excessive APAP use may compromise early placental development and pregnancy outcomes.</p><p><strong>Abstract: </strong>Extravillous trophoblast (EVT) cell invasion is crucial for the establishment of proper maternal-fetal circulation and successful pregnancy outcomes. Acetaminophen (APAP) is commonly used as the first-line analgesic during pregnancy, yet its potential effects on placental function are not well understood. In this study, we investigated the effects of APAP at therapeutic (0.1 and 0.5 mM) and overdose (1, 2, and 5 mM) concentrations on the expression of matrix metalloproteinase 2 (MMP2), a key enzyme involved in extracellular matrix degradation and EVT cell invasion, and explored the underlying molecular mechanisms in human EVT cells. Our results showed that therapeutic doses of APAP did not alter MMP2 expression, whereas overdose concentrations significantly suppressed EVT cell invasion by downregulating MMP2. We further demonstrated that this suppression of MMP2 was mediated by the inhibition of AKT signaling, leading to reduced expression of SP1, a transcription factor critical for MMP2 regulation. Given the critical role of EVT cell invasion in early placental development, our findings provide new insights into how APAP overdose may disrupt EVT function and potentially impact pregnancy outcomes.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144744556","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":"Sustained YAP1 signaling alters the fates of lutein and Müllerian mesenchymal cells in mice.","authors":"Michael Bérubé, Samuel Gusscott, Junhao Mao, Gustavo Zamberlam, Alexandre Boyer, Guillaume St-Jean, Julie Brind'Amour, Derek Boerboom","doi":"10.1530/REP-24-0450","DOIUrl":"10.1530/REP-24-0450","url":null,"abstract":"<p><strong>In brief: </strong>The Hippo signaling pathway plays crucial roles in various processes related to development and tissue homeostasis. This study demonstrates that sustained YAP1 activity can influence cell fate within the reproductive system, specifically in lutein and Müllerian mesenchymal cells, causing them to transdifferentiate into myofibroblasts.</p><p><strong>Abstract: </strong>Recent reports have suggested that the Hippo intracellular signaling pathway is required for homeostasis in a variety of tissues, including the ovary and female reproductive tract. To further define the role of the Hippo effector YAP1 in the female reproductive system, transgenic mouse models were designed to direct the expression of a dominant stable mutant form of YAP1, termed YAP5SA, to the granulosa cells of antral follicles (R26YAP5SA ;CYP19-cre) and Müllerian mesenchymal cells (R26YAP5SA ;Amhr2 cre/+). Unexpectedly, YAP5SA expression in the ovaries of R26YAP5SA ;CYP19-cre mice was not detected in granulosa cells, but rather in a subset of lutein cells. This caused the lutein cells to transdifferentiate into cells having the morphologic and functional properties of myofibroblasts, including collagen deposition. These cells coalesced into roughly spherical lesions that persisted in the ovaries, but did not interfere with ovarian function or fertility. Seminiferous tubule-like structures also formed in the ovaries of adult R26YAP5SA ;CYP19-cre mice, containing SOX9-positive Sertoli-like cells but no germ cells. Although multi-lineage transdifferentiation had been reported in mice lacking the Hippo kinases Lats1 and -2 in their granulosa cells, comparative transcriptomic analyses of granulosa cells expressing YAP5SA vs granulosa cells lacking Lats1/2 showed few similarities in transcriptome alterations. R26YAP5SA ;Amhr2 cre/+ mice had severe developmental defects of their reproductive tracts, which were attributed to the transdifferentiation of Müllerian mesenchymal cells into myofibroblasts during embryogenesis. Together, these results indicate that sustained YAP1 signaling induces transdifferentiation in lutein and Müllerian mesenchymal cells, and further underscores the role of Hippo signaling in the maintenance of their fates.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637894","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":"Epicatechin inhibits inflammatory injury in preeclampsia extravillous trophoblasts.","authors":"Mengyongwei Li, Mian Liu, Jiaoqi Mei, Haofu Dai, Huiqin Chen, Qiuling Jie, Jingjing Mei, Xiaohui Yang, Jinyu Kang, Yanlin Ma, Wenli Mei","doi":"10.1530/REP-24-0182","DOIUrl":"https://doi.org/10.1530/REP-24-0182","url":null,"abstract":"<p><strong>In brief: </strong>Preeclampsia is a severe pregnancy-related complication that can result in adverse maternal and fetal outcomes. Current therapeutic options for preeclampsia remain limited. This study demonstrates that epicatechin can inhibit pyroptosis in extravillous trophoblasts and block the activation of the NF-κB signaling pathway, thereby offering a novel therapeutic approach for the management of preeclampsia.</p><p><strong>Abstract: </strong>Preeclampsia (PE) is characterized as new-onset hypertension and proteinuria after 20 weeks of gestation, and affects 5%-7% pregnant women globally. PE is associated with a systemic inflammatory status that is overly activated and contributes to dysregulated extravillous trophoblasts (EVTs) invasion and impaired spiral vessel remodeling. Recent studies showed that inhibition of systematic inflammatory response significantly ameliorates the PE-like symptoms, suggesting that anti-inflammation could be a potential PE treatment. However, few effective therapeutic strategies have been shown to control systemic inflammation in PE patients. In the current study, we investigated the protective effects of epicatechin (EC), one small molecule compound that exhibits excellent anti-inflammatory activity, on HTR8/SVneo cells and EVTs stimulated with lipopolysaccharide (LPS). Our results revealed that EC pretreatment significantly improved cellular viability and attenuated the inflammatory response of EVTs in response to LPS stimulation. Mechanistically, we found that EC significantly blocked the activation of the LPS-induced pyroptosis pathway of classical pyrin domain protein 3, cleaved caspase 1 and cleaved gasdermin D (NLRP3/Caspase-1/GSDMD) in LPS-treated EVTs and inhibited interleukin-1β (IL-1β) expression (a hallmark of pyroptosis) by suppressing the nuclear factor-κB (NF-κB) signaling. Our study demonstrates the protective effects of EC on LPS-stimulated and provide the direct evidence in vitro that EC may be a promising compound that mitigates the PE-associated systemic inflammation.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637891","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":"Divergence in the sow vaginal microbiota is associated with fertility.","authors":"Lauren Fletcher, Xiaoshu Zhan, Yashu Song, Julang Li","doi":"10.1530/REP-25-0044","DOIUrl":"10.1530/REP-25-0044","url":null,"abstract":"<p><strong>In brief: </strong>Vaginal microbiota composition influences female fertility, however it has not been studied for measuring fertility level in female pigs. This study reveals significant vaginal microbiota composition differences between high reproductive performance and infertile sows, and demonstrates that the vaginal microbiota has promise for improving female pig selection using machine learning modeling.</p><p><strong>Abstract: </strong>There is a need for reliable and effective biomarkers of female fertility and reproductive potential in the pork industry, as current selection protocols are not keeping up with the rate of improvement for other production-related traits. This study aimed to investigate the vaginal microbiota composition between sows of differing fertility status and identify candidate vaginal microbiota biomarkers of sow fertility. The vaginal microbiota of high reproductive performance sows (HRP, n = 52) with number of piglets born alive ≥13 and infertile sows (INF, n = 23), that remained nonpregnant after two consecutive rounds of artificial insemination, were investigated. Sequencing results revealed significantly different (P < 0.05) beta diversity at the genus level between HRP and INF vaginal microbiota communities. Accordingly, the composition of the vaginal microbiota diverged between HRP and INF sows, with INF sows having increased (P < 0.05) relative abundance of Lachnospiraceae XPB1014 group and HRP sows having increased (P < 0.05) relative abundance of Aerococcus and Staphylococcus at the genus level. Forty-two genera were selected as candidate biomarkers of sow fertility via partial least squares discriminant analysis (PLS-DA) and recursive feature elimination. The support-vector machine model classified sow fertility with 93.3% accuracy, supporting potential industry application to improve upon current methods for selection and recruitment in the breeding herd. Future investigations should validate the candidate vaginal microbiota biomarkers in a large, independent population of sows and gilts to evaluate their application for predicting future reproductive performance and assess their true industry applicability.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226452","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":"Disrupted MOS signaling alters meiotic cell cycle regulation and the egg transcriptome.","authors":"Gisela Cairo, Olha Kholod, Olivia Palmer, Sophia Meytin, Brittany A Goods, Soni Lacefield","doi":"10.1530/REP-25-0156","DOIUrl":"10.1530/REP-25-0156","url":null,"abstract":"<p><strong>In brief: </strong>Through the precise coordination of meiosis, the oocyte gives rise to a mature egg that is competent to support fertilization and initiate embryonic development. This study reveals that MOS signaling is critical for proper meiotic regulation and for maintaining the egg in a transcriptionally inactive state.</p><p><strong>Abstract: </strong>Mammalian female meiosis is tightly regulated to produce a developmentally competent egg. Oocytes enter meiosis in the fetal ovary and then arrest at prophase I until sexual maturation. Upon hormonal stimulation, a subset of oocytes resumes meiosis. Oocytes then complete meiosis I, enter metaphase II and arrest until fertilization, a process essential for egg competency. The MOS kinase is a key regulator of the metaphase II arrest, activating the MAPK signaling cascade. Loss of MOS in female mice disrupts the maintenance of the metaphase II arrest, with some eggs extruding two polar bodies and some dividing beyond anaphase II. To investigate the consequences of the Mos deletion, we performed live imaging and found that mos-/- eggs exhibit transient chromosome separation events in meiosis I, suggesting a role for MOS in coordinating the timing of meiotic divisions. Further analysis showed that new transcription is required for mos-/- eggs to undergo additional divisions but not for second polar body (PB) extrusion. Surprisingly, single-egg sequencing revealed extensive differences in gene expression between wild-type (WT) and mos-/- eggs, including those with only one PB. Many differentially expressed genes were involved in cell cycle regulation, including Aurka, Bub3 and Cdk7. Upregulated pathways included metabolism of RNA, transcription and neddylation. Furthermore, the gene expression profile of mos-/- eggs was markedly different from that of chemically activated WT eggs. Our findings demonstrate that MOS plays a crucial role in meiotic cell cycle regulation and helps ensure that the egg maintains the proper transcriptome necessary for developmental competence.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151462","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":"PREGNANCY DISORDERS AND MATERNAL CONSEQUENCES: Maternal pre-pregnancy risks and postpartum consequences of gestational diabetes.","authors":"Kathryn M Storey, Lena Shay, Truman Poteat, Kathleen A Pennington, Laura C Schulz","doi":"10.1530/REP-25-0050","DOIUrl":"10.1530/REP-25-0050","url":null,"abstract":"<p><strong>In brief: </strong>Maternal morbidities both unmodifiable (genetics and prior history) and modifiable (insulin resistance and obesity) are associated with gestational diabetes. This review discusses common risk factors and postpartum consequences.</p><p><strong>Abstract: </strong>Gestational diabetes mellitus (GDM) is defined by the World Health Organization (WHO) as glucose intolerance of varying severity with first recognition or onset during pregnancy. It can be caused by excess insulin resistance, a failure to augment insulin secretion in response to pregnancy, or both. The risk of developing GDM is affected by several maternal morbidities, some of which are modifiable. Personal or family history of GDM or type 2 diabetes is strongly associated with GDM, and some susceptibility alleles for type 2 diabetes are shared with GDM. Social determinants of health including access to care and nutritional availability are also associated with GDM risk. Obesity is particularly associated with insulin resistance and dyslipidemia, which are risk factors for GDM. These factors are also present in polycystic ovarian syndrome (PCOS), and women with this condition have an elevated risk of GDM. While dysfunctional beta cell compensation may also be present before pregnancy and predispose to GDM, symptoms only manifest in pregnancy. Other factors that may increase the risk of GDM include folic acid supplementation, age of either of the parents and interpregnancy interval. Not only are preexisting maternal morbidities associated with the development of GDM, but women who have experienced a pregnancy complicated by GDM are more likely to develop type 2 diabetes and cardiovascular disease later in life. Whether this relationship is cause-and-effect or due to common underlying risk factors is unknown.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079956","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":"Hippo signaling in mammalian reproduction.","authors":"Robin E Kruger, Farina Aziz, Amy Ralston","doi":"10.1530/REP-25-0016","DOIUrl":"10.1530/REP-25-0016","url":null,"abstract":"<p><p>The Hippo signaling pathway, so named for its massive overgrowth mutant phenotypes, has become one of the most exciting signaling pathways to emerge in the field of reproductive biology. While disruption of Hippo is associated with tumorigenesis in many organs and tissues, relatively less is understood about the normal roles of Hippo signaling in the reproductive organs. Here, we highlight the recent literature illuminating the roles of Hippo pathway members in mouse and human reproduction. We place special emphasis on the inputs and outputs of Hippo signaling during preimplantation development, where Hippo signaling has been extensively studied in both mouse and human. We note a common emerging theme is the critical and highly conserved role of Hippo signaling in epithelia of the reproductive organs. We also discuss human reproductive disorders, whose etiology may be related to dysregulation of Hippo signaling, and possible therapies that have been proposed to correct this dysregulation. Finally, we describe the edge of our knowledge, which currently limits our understanding of Hippo signaling in reproductive health and disease.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079953","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":"POLYCYSTIC OVARY SYNDROME: ORIGINS AND IMPLICATIONS: The significance of functional adrenal hyperandrogenism in polycystic ovary syndrome across the lifespan.","authors":"Laura C Torchen, Margaret Wu, Brianna Thompson, Andi Beaudouin","doi":"10.1530/REP-25-0091","DOIUrl":"10.1530/REP-25-0091","url":null,"abstract":"<p><strong>In brief: </strong>The adrenal glands are an additional source of hyperandrogenemia in a significant proportion of women with polycystic ovary syndrome (PCOS). This review presents the evidence for the role of adrenal hyperandrogenism in the development and clinical manifestations of the syndrome across the lifetime.</p><p><strong>Abstract: </strong>Functional adrenal hyperandrogenism is a common feature of PCOS, observed in roughly 20-30% of affected women. The mechanisms of adrenal hyperandrogenism in PCOS require additional clarification but seem to be related to increased adrenal sensitivity to ACTH at the level of the adrenal gland. Studies in animal models and in girls at risk for PCOS suggest a potential role for early adrenal androgen exposure in the development of PCOS during reproductive maturity. Importantly, adrenal androgens may be elevated in at-risk girls from childhood through menopause, suggesting these androgens are clinically relevant over the lifetime. The presence or absence of adrenal hyperandrogenism is just one of a number of clinical phenotypes, which vary among women with PCOS. Recent exciting work has focused on defining distinct subtypes of PCOS based on these distinct phenotypes. This will be an important first step toward the development of more individualized treatment approaches in affected women.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079959","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}