Reproductive Sciences最新文献

{"title":"Downregulation of FOXO1 in PCOS Granulosa Cells: A Direct Target of microRNA-183.","authors":"Tingting He, Xia Xue, Juanzi Shi","doi":"10.1007/s43032-025-01886-8","DOIUrl":"https://doi.org/10.1007/s43032-025-01886-8","url":null,"abstract":"<p><p>The purpose of this study is to investigate whether microRNA (miR-183) and forkhead box O1 (FOXO1) are abnormally expressed in polycystic ovary syndrome (PCOS) granulosa cells (GCs) and further explore its underlying molecular mechanisms. The expressions of miR-183 and FOXO1 in GCs isolated from 55 PCOS and 60 control patients were determined by quantitative reverse transcription-polymerase chain reaction (q-PCR) and western blot respectively. Granulosa-like tumor cell line (KGN) cells were used to alter the levels of miR-183 and FOXO1 by transfection. The target genes of miR-183 were first predicted by bioinformatics analysis and then verified by q-PCR, western blot and luciferase reporter assay. KGN cells were treated by insulin to further verify the relationship between miR-183 and FOXO1. The results demonstrated that the expression of miR-183 was significantly increased in PCOS patients, while FOXO1 was decreased. In addition, FOXO1 was a direct target of miR-183, which was negative with homeostasis model assessment for insulin resistance (HOMA-IR). Moreover, insulin treatment in KGN cells induced upregulation of miR-183 and decreased FOXO1. It could be speculated that insulin-mediated miR-183 targets FOXO1 to regulate the pathogenesis of PCOS, which might provide a new idea for investigating the functional role of miR-183 in PCOS GCs.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in the Pathophysiology of Thin Endometrium.","authors":"Yifei Niu, Aiwen Le","doi":"10.1007/s43032-025-01882-y","DOIUrl":"https://doi.org/10.1007/s43032-025-01882-y","url":null,"abstract":"<p><p>A thin endometrial lining, typically defined as an endometrial thickness of less than 7 mm, is commonly associated with failed embryo implantation, recurrent pregnancy loss, and infertility. This review summarizes the current understanding of the pathophysiological mechanisms underlying thin endometrium and highlights emerging therapeutic approaches. Published studies indicate that impaired uterine perfusion and downregulation of vascular endothelial growth factor (VEGF) compromise angiogenesis, resulting in tissue-level reproductive defects. Hypoxia, together with the activation of the hypoxia-inducible factor 1-alpha (HIF-1α) and RhoA/Rho-associated protein kinase (ROCK) pathways, has been shown to disrupt epithelial cell integrity and exacerbate endometrial atrophy. Immune impairments characterized by abnormal cytokine signaling, reduced natural killer (NK) cell activity, and chronic endometritis further reduce endometrial tolerance. Additionally, epigenetic modifications, such as aberrant DNA methylation and microRNA (miRNA) dysregulation, have been linked to altered expression of key implantation-related genes, including homeobox A10 (HOXA10). Conventional therapies, such as estrogen supplementation, vasodilators, and granulocyte colony-stimulating factor (G-CSF), have variable efficacy. In contrast, regenerative strategies, including stem cell-based therapies, platelet-rich plasma (PRP), and biomaterial-based interventions, have shown promising potential for restoring endometrial function. A comprehensive understanding of these mechanisms is essential for improving diagnostic and therapeutic strategies, and while regenerative approaches represent a promising avenue for enhancing endometrial receptivity and reproductive success, further preclinical and clinical studies are warranted to optimize these novel therapies and evaluate their long-term safety and efficacy.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CHIR99021 Enhances the Proliferation of Mouse Female Germline Stem Cells Via Modulating ERCC2.","authors":"Qingling Jia, Geng G Tian, Xiaoyong Li, Ji Wu","doi":"10.1007/s43032-025-01877-9","DOIUrl":"https://doi.org/10.1007/s43032-025-01877-9","url":null,"abstract":"<p><p>Female germline stem cells (FGSCs) are a type of adult stem cell that exist in mammalian ovaries and can self-renew and differentiate into mature oocytes. Small molecule compounds are substances with a molecular weight less than 900 Daltons that can affect cellular functions and behaviors through various mechanisms. Here, we identified three compounds, Agrin, CHIR99021 (CHIR), and Testosterone, that can enhance the proliferation of FGSCs, with CHIR demonstrating superior efficacy. To elucidate the mechanism underlying CHIR's role in promoting FGSCs proliferation, we conducted RNA sequencing and tandem mass tag (TMT)-based quantitative proteomic profiling on FGSCs both with and without CHIR exposure. By integrating the data from these two sequencing approaches, we employed gene set enrichment analysis (GSEA) and identified Ercc2 as a crucial gene modulated by CHIR-induced FGSC proliferation. Further experiments confirmed that CHIR enhanced FGSCs proliferation via ERCC2. This research deepens our comprehension of the proliferative mechanisms of FGSCs and lays a theoretical foundation for future investigations into the developmental mechanisms of female germ cells, as well as the development of infertility treatments.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating Cell Free microRNAs in Women with Polycystic Ovary Syndrome: Advancing Towards Biomarker Discovery and Therapeutic Targets.","authors":"Palaniswamy Ramaswamy, Pratibha Misra, Ruchira Godse, Anurodh Gupta, Nikita Naredi, Sibin Mk, Ankita Gambhirrao, Bhasker Mukherjee, Yaongamphi Vashum","doi":"10.1007/s43032-025-01872-0","DOIUrl":"https://doi.org/10.1007/s43032-025-01872-0","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is the most common metabolic and endocrine disorder affecting women of reproductive age. This condition is characterized by the presence of polycystic ovarian morphology, anovulation, and clinical or biochemical manifestations of hyperandrogenism. Numerous patients diagnosed with PCOS also experience conditions such as obesity, hirsutism, insulin resistance, and an elevated risk of developing type 2 diabetes, dyslipidemia, hypertension, cardiovascular disease, endometrial cancer, as well as infertility and complications during pregnancy. While the precise etiology remains unidentified, it is widely acknowledged that genetic, environmental, and epigenetic factors contribute to the pathogenesis of PCOS. This review consolidates findings from various studies that investigated circulating microRNAs (miRNAs) as potential diagnostic biomarkers for PCOS, illustrating both their promise and the challenges associated with clinical implementation. We address the obstacles pertaining to standardization, explore the diagnostic potential of statistically significant miRNAs across multiple biofluids, including plasma, serum, follicular fluid, and blood, and present a graphical overview of overlapping miRNAs accompanied by a table summarizing key findings. With further validation, miRNAs hold the potential not only to improve the diagnostic processes for PCOS but also to facilitate the development of novel therapeutic interventions for the management of this disorder.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of AMH on Folliculogenesis.","authors":"Mei Lv, Anni Feng, Di Cheng, Zejun Xu, Yuanjie Xie, Jian Tu","doi":"10.1007/s43032-025-01879-7","DOIUrl":"https://doi.org/10.1007/s43032-025-01879-7","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a common and frequent disease and always leads to endocrine and metabolic disorders among women of reproductive age. In most PCOS patients, the serum level of anti-mullerian hormone (AMH) is significantly higher than that of normal women of childbearing age. AMH is an important auxiliary diagnostic method for PCOS. AMH may play an important role in the occurrence and development of PCOS and potentially affect the success of in vitro fertilization (IVF) treatments, although the exact mechanisms remain unclear. This review focuses on the relationships and mechanisms of dysregulated AMH and follicular development in PCOS based on recent research. It is mainly manifested in the regulation of related signal pathways, the negative feedback regulatory loop of several gonadal hormones such as follicle-stimulating hormone, luteinizing hormone, estradiol, and testosterone, as well as the influence of AMH on IVF in PCOS patients. Additionally, it puts forward some suggestions, which will provide some helpful ideas or directions for future further research on PCOS.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adverse Maternal and Fetal Outcomes Associated with Insomnia During Pregnancy: a Systematic Review and Meta-Analysis.","authors":"Dongmei Liu, Shujie Guo, Cunmei Tan, Ke Zhang, Yuxuan Feng, Xiaoxuan Bi, Jingjing Jiang, Wei Yang, Yanhong Wang","doi":"10.1007/s43032-025-01849-z","DOIUrl":"https://doi.org/10.1007/s43032-025-01849-z","url":null,"abstract":"<p><p>Insomnia affects most pregnant women. This systematic review aims to examine regarding gestational insomnia and its consequences on pregnant women and neonates. We performed a systematic search of seven databases for English and Chinese language articles about the association between insomnia and maternal complications and adverse fetal outcomes from inception to July 2022 then updated the search date to April 2024. We included observational studies concerning gestational insomnia and one or more adverse maternal, delivery, or neonatal outcomes. Data extraction was completed independently by two reviewers. The quality assessment was analyzed with the Newcastle-Ottawa quality assessment scale and an 11-item checklist recommended by Agency for Healthcare Research and Quality for observational cohort and cross-sectional studies. Data analysis was carried out through meta-analysis and narrative synthesis. Twenty-three identified studies (fifteen cohort studies, six cross-sectional studies and two case-control studies) examined the associations of gestational insomnia with adverse maternal and infant outcomes. The most consistent associations were observed between gestational insomnia and increased risks of perinatal depression (OR = 2.30, 95%CI:1.77,2.96, P = 0.002), perinatal anxiety and postpartum pain. There were mixed findings for post-traumatic stress disorder and low birth weight. Gestational insomnia was not associated with cesarean delivery (OR = 0.92, 95%CI: 0.61,1.38, P = 0.328), gestational hypertension (OR = 1.06, 95%CI: 0.90,1.25, P = 0.526), pre-eclampsia (OR = 1.67, 95%CI:0.21,13.44, P = 0.01), gestational diabetes (OR = 0.77, 95%CI: 0.48,1.24, P = 0.78), preterm birth (OR = 1.09, 95%CI:0.75,1.58, P = 0.073), high birth weight or low Apgar scores. There is an association between insomnia and some adverse maternal and infant outcomes, but larger samples and well-designed prospective studies are still needed to determine their relationship in the future.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Evaluation of an Updated Gene Panel as a Diagnostic Tool for Both Male and Female Infertility.","authors":"Özlem Okutman, Ali Sami Gürbüz, Ahmet Salvarci, Umut Büyük, Halil Ruso, Timur Gürgan, Julien Tarabeux, Anne-Sophie Leuvrey, Elsa Nourisson, Cécile Lang, Jean Muller, Stephane Viville","doi":"10.1007/s43032-025-01881-z","DOIUrl":"https://doi.org/10.1007/s43032-025-01881-z","url":null,"abstract":"","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impairment of Oogenesis and Folliculogenesis in Neonatal Rats after Maternal Exposure to Mobile Phones.","authors":"Behpour Yousefi, Majid Jadidi, Zahra Nabizadeh, Mohammad Hasan Tabrizi Amjad, Maryam Ardekanian","doi":"10.1007/s43032-025-01880-0","DOIUrl":"https://doi.org/10.1007/s43032-025-01880-0","url":null,"abstract":"<p><p>Today's lifestyle has led to an increase in infertility. The study investigated the effects of cell phone radiation on oogenesis, folliculogenesis, and gestation stage. Also, its impact on neonates' ovarian hormones and their ovarian development during gestation was investigated. Fifty-four virgin female Wistar rats were randomly divided into three groups: the study group (conversation and stand-by mode, n = 24), the control group (stand-by mode, n = 24), and the sham (turn off, n = 6). The study and control groups were separated into 4 subgroups, including early stage (1st week), mid-stage (2nd week), late stage (3rd week), and all stages (3 weeks). The results showed that the concentration of plasma estrogen and progesterone, ovarian primordial follicle/primary oocyte, the number of primordial follicles, and nuclei diameters in the study and control subgroups decreased significantly in comparison with the sham group. The most significant reduction was observed in subgroups in which mothers were exposed to radiation for a long period during their pregnancy. Compared to the control and sham groups, the number of primordial follicle apoptosis markedly increased in the study subgroups. The pregnant rats showed significant effects in the entire stages of pregnancy, especially during the first stage (the first week) of development, which has not been reported previously. Exposure to cell phones during the different gestation stages probably decreases ovarian hormone secretion and may harm oogenesis. It also inversely increases the apoptosis of primordial follicles. Therefore, the gestational stages and duration of exposure to cell phone radiation affect the risk of ovarian harm.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Factors of Oncologic and Reproductive Outcomes in Conservative Therapy of Endometrial Hyperplasia and Endometrial Cancer: Systematic Review and Meta-Analysis.","authors":"Ling He, Jiayu Wei, Dan Kuai, Dongcan Zhang, Yanfang Zhang, Wenyan Tian, Huiying Zhang, Yingmei Wang","doi":"10.1007/s43032-025-01874-y","DOIUrl":"https://doi.org/10.1007/s43032-025-01874-y","url":null,"abstract":"<p><p>Despite broad consensus on the oncological criteria for the inclusion of patients in conservative therapy for endometrial cancer (EC), several prognostic factors affecting patients' subsequent oncological and reproductive outcomes have yet to be explored. To assess the prognostic factors influencing remission, pregnancy and recurrence in conservative therapy of endometrial hyperplasia (EH) and EC. Following the PRISMA statement and the Cochrane Handbook, the search for relevant studies was conducted in PubMed, Embase, Web of Science, Wan fang and China National Knowledge Infrastructure from the inception of the databases to 1 March 2024. Studies that met the inclusion criteria were evaluated for quality using the Newcastle-Ottawa Scale and subsequently analyzed for data extraction. This meta-analysis included 3815 patients with EC or EH treated with conservative therapy in 35 studies. The analysis revealed the overall remission rate of 92.0% (95% CI, 87.0-96.0%), pregnancy rate of 34.0% (95% CI, 32.0-36.0%), and recurrence rate of 27.0% (95% CI, 25.0-29.0%). Four study characteristics, including obesity, pathology type, lesion size, and insulin resistance were associated with remission rate. A total of 8 study characteristics were found to be associated with pregnancy rate, including obesity, pathology type, time to complete response (CR), mode of conception, intrauterine adhesion, the number of uterine manipulations, endometrial thickness and recurrence before pregnancy. Seven study characteristics were found to be associated with recurrence rate, including age over 35.0 years, obesity, family history of cancer, pathological type, abnormal menstruation, pregnancy and maintenance treatment after CR. Common prognostic factors affecting remission, pregnancy and recurrence of endometrial cancer and endometrial hyperplasia are obesity and type of pathology. Patient characteristics, medical factors, and pathological features significantly influence oncological and reproductive outcomes in patients with EH and EC undergoing conservative therapy. Consequently, careful clinical selection and individualized assessment of each candidate for conservative therapy are essential to optimally balance short-term oncological and reproductive outcomes with long-term survival prognosis.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"17beta-estradiol (E2) Regulates Malignancies and Stemness in Endometrial Carcinoma (EC) via Interacting with ESR1.","authors":"Xiaochao Xu, Xinzhi Dai, Cheng Huang, Xia Guan, Cuiwei Zhang","doi":"10.1007/s43032-025-01871-1","DOIUrl":"https://doi.org/10.1007/s43032-025-01871-1","url":null,"abstract":"<p><p>Endometrial cancer is one of the most common and fatal gynaecologic malignancies and is associated with the presence of estrogen. Endometrial cancer stem-like cells (ECSCs) are stem-like cell subpopulations endowed with self-renewal and differentiation capacities and are critical for EC progression. However, it is still unknown whether estrogen is involved in regulating stemness in EC and contributes to malignancies. Therefore, we investigated the regulatory effects of E2 treatment on oestrogen receptor-1 (ESR1).ESR1 expression was measured in EC tissues; After ESR1 overexpression of knockdown, the effects of E2 treatment was evaluated, including cell proliferation, sphere formation, invasion and colony formation. Our results indicate that ESR1 is critical for the regulatory effect of E2 on EC cells. After being cultured in serum-free medium, the ECSCs were found to be enriched in stemness markers, including CD133, CD44 and ALDH1. Interestingly, enriched ECSCs presented significantly lower expression levels of these factors than the parental cells. Overexpression of ESR1 slightly affected stemness and malignant potential in ECSCs, and the addition of 2 nM E2 markedly decreased stemness and inhibited malignant behaviours of ECSCs, including proliferation, invasion and tumour formation, in soft agar. Moreover, the addition of E2 significantly inhibited the expression of epithelial-mesenchymal transition (EMT) markers, including ZEB1, ZEB2, and E-cadherin.ESR1 is critical for regulating EC progression in the presence of E2, partially by regulating stemness in ECSCs, indicating that ESR1 might be a potential therapeutic target for EC.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}