Reproductive Sciences最新文献

{"title":"Role of Estrogen Signaling in Notch Pathway Activation in Sertoli Cells.","authors":"Sylwia Lustofin, Alicja Kamińska, Barbara Bilińska, Julia Wajda, Anna Hejmej","doi":"10.1007/s43032-025-01901-y","DOIUrl":"10.1007/s43032-025-01901-y","url":null,"abstract":"<p><p>Sertoli cells constitute a somatic component of seminiferous epithelium in mammalian testis which supports the process of spermatogenesis. These cells are sensitive not only to the male sex hormones androgens, but also to their metabolites, estrogens. In this study, we aimed to explore the action of estrogen signaling in rodent Sertoli cells on the activity of canonical Notch pathway, which provides contact-dependent communication between the cells of seminiferous epithelium. Experiments performed on Sertoli cell line and primary Sertoli cell cultures demonstrated that 17β-estradiol, acting through estrogen receptor 2, enhances Notch1 activation, transcriptional activity of recombination signal binding protein for immunoglobulin kappa J region (RBPJ), interaction of RBPJ with Hes1 promoter, and the expression of the Hes1 effector gene and protein. On the other hand, 17β-estradiol by binding to estrogen receptor 1 reduces the expression of the Hey1 effector gene. In contrast to nuclear estrogen receptors, no evident role of G protein-coupled estrogen receptor 1 in regulating Notch1 signaling activity in Sertoli cells has been found. The data presented indicate the role of nuclear estrogen receptor signaling in the control of Notch1 pathway activity in Sertoli cells, and thus reveal new mechanism of estrogen action in maintaining homeostasis of the seminiferous epithelium.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2307-2318"},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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":"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":"2467-2473"},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","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":"Predictive Screening for Inflammatory Disorders of Pregnancy Using Targeted Maternal Cell-Free RNA Assays: Proof-of-Principle Data from Large Animal and Human Cohorts.","authors":"Sean W D Carter, Qin Wei, Winston Koh, Xiawen Liu, Kay Yi Michelle Seah, Si En Poh, Haruo Usuda, Erin L Fee, Yusaku Kumagai, Tsukasa Takahashi, Lara Monteiro, Reyna Peñailillo, Hannah R S Watson, Masatoshi Saito, Owen B Spiller, Mahesh A Choolani, Sebastián E Illanes, Matthew W Kemp","doi":"10.1007/s43032-025-01876-w","DOIUrl":"10.1007/s43032-025-01876-w","url":null,"abstract":"<p><p>The management and prevention of key inflammatory-associated pregnancy complications such as chorioamnionitis and pre-eclampsia is hampered by a lack of early gestation risk screening tools. In a proof-of-principle study we used targeted cell-free RNA analyses of maternal plasma samples from large animal (sheep) and human pregnancy cohorts to develop a minimally invasive screening test for inflammatory markers. This study utilised a preterm sheep model of sterile and bacterial chorioamnionitis. Date-mated ewes received either intraamniotic Saline Control (n = 10) or E.Coli LPS (Sterile chorioamnionitis) with 2 days (n = 9) or 8 days exposure(n = 6). Preterm lambs were delivered at 124 ± 1d gestation. Findings were validated in a bacterial model of chorioamnionitis where ewes were exposed to 7 days of intraamniotic M.Hominis with delivery at 98 d gestion(n = 8) or 128d gestation(n = 8). Maternal blood was collected prior to intervention and at delivery in each group. Random Forest algorithm was used to analyse 8 cell-free RNA(cfRNA) targets related to inflammation in maternal plasma at baseline and delivery, identifying genes that separated animals with or without intrauterine inflammation. Plasma cfRNA data was compared to mRNA expression in placental tissue. Haematological and placental mRNA comparisons were analysed with ANOVA/Tukey HSD/Dunnett T3 tests. Maternal plasma cfRNA findings of intrauterine inflammation were then validated in human plasma samples from a cohort of patients with late onset pre-eclampsia (n = 10) or uncomplicated pregnancies (n = 10). We present data showing that targeted maternal cfRNA assays can accurately identify chorioamnionitis of sterile (AUC 1.0) and infectious (AUC 0.84) origin in a sheep model of pregnancy. Findings were then validated in human maternal plasma samples from patients with late-onset pre-eclampsia in the 1st (AUC = 0.85), 2nd (AUC = 0.90) and 3rd (AUC = 0.82) trimesters. In both sheep and human model systems, cfRNA tests offered high levels of sensitivity and specificity in the absence of overt clinical symptoms. We suggest that further development of this technology may serve as a scalable, rapidly deployed and cost-effective means for predicting major inflammatory conditions in pregnancy.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2340-2361"},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic Profiling Reveals Potential Genes Involved in the Immune Landscape of Polycystic Ovary Syndrome: An Exploratory Study.","authors":"Ye Zhang, Zhiyang Hu, Zebo Cai, Junda Lai, Huiqiong Zeng","doi":"10.1007/s43032-025-01917-4","DOIUrl":"10.1007/s43032-025-01917-4","url":null,"abstract":"","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2404-2422"},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategic Guidelines to Integrate Artificial Intelligence in Obstetrics and Gynecology: Best Practices and Ethical Considerations.","authors":"Pallav Sengupta, Sulagna Dutta, Sovan Bagchi, Prashanth Hegde, Suraj Sebastian, David Cm Taylor, Ralf Henkel","doi":"10.1007/s43032-025-01903-w","DOIUrl":"10.1007/s43032-025-01903-w","url":null,"abstract":"<p><p>The transformative advancements in artificial intelligence (AI) have significantly impacted medical fields, particularly obstetrics and gynecology (OBGYN). This manuscript presents a comprehensive set of twelve strategic guidelines for the effective integration of AI into OBGYN, emphasizing both best practices and ethical considerations. These guidelines cover essential domains including multidisciplinary collaboration, safeguarding patient safety and privacy, continuous staff training, mitigating algorithmic bias, promoting transparent communication with patients, and fostering a continuous feedback loop between clinicians and AI developers. Additional recommendations highlight the importance of staying updated on AI advancements, defining the role of AI within clinical governance frameworks, ensuring long-term sustainability, collaborating with AI vendors for customized solutions, and evaluating outcomes to inform future practice. These strategies are designed to position AI as an augmentative tool in clinical decision-making, ensuring it enhances rather than replaces human expertise. By upholding collaborative efforts and ethical standards, AI can profoundly improve care quality in OBGYN, fostering safer and more effective healthcare delivery.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2244-2251"},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310421","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":"A Novel De Novo KAT6B Mutation Causes Hypospadias in a Chinese Fetus at 29 Weeks Gestation.","authors":"Xue Zhong, Meixin Liu, Qun Gao, Monong Li, Shiguo Liu","doi":"10.1007/s43032-025-01860-4","DOIUrl":"10.1007/s43032-025-01860-4","url":null,"abstract":"<p><p>KAT6B mutations are responsible for Say-Barber-Biesecker-Young-Simpson syndrome or Genitopatellar syndrome, with most mutations occurring in its exon 18. A pregnancy with normal early antenatal examination revealed the presence of hypospadias in the fetus but with no abnormal amniotic fluid volume in ultrasonography at 29th^+ 4d weeks' gestation. After amniocentesis, the trios' whole exome sequencing was performed and a novel frameshift mutation (KAT6B: exon10: c.2153_2159del, p. R718Lfs*3) was identified for her fetus, then verified by the parents as a de novo mutation. Following this couple's decision to induce labor, the appearance of the fetus had hypospadias but with a normal face and was able to be palpated for the patella. KAT6B mutations often occur with a variety of symptoms. To our acknowledgment, this is the first report of a novel de novo KAT6B mutation causing only hypospadias for the fetus, which further expands the spectrum of KAT6B variants and the genotype-phenotype relationship for this disease.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2252-2258"},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050869","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":"Metformin Improves Palmitate-Induced Follicular Granulosa Cell Dysfunction by Activating ULK1-Mediated Autophagy.","authors":"Nuo Heng, Haisheng Hao, Yingfan Hu, Yi Wang, Huan Wang, Wei He, Ni Zhu, Rui Wang, Xiuli Xuan, Huabin Zhu, Shanjiang Zhao, Feng Wang","doi":"10.1007/s43032-025-01894-8","DOIUrl":"10.1007/s43032-025-01894-8","url":null,"abstract":"<p><p>Obesity has become a global epidemic with major implications for fertility. In particular, obesity can trigger follicular atresia by initiating the apoptosis of granulosa cells (GCs). Emerging evidence suggests that this process may be closely linked to the dysregulation of cellular autophagy. Metformin has been shown to restore autophagic flux and mitigate obesity-related cellular dysfunction in mice; however, the ability of metformin to alleviate lipid overload-induced damage in goat granulosa cells has yet to be investigated. Analyses showed that 400 μM palmitic acid (PA) significantly increased lipid accumulation and reduced cell viability (P < 0.05) in goat granulosa cells. Furthermore, PA impaired mitochondrial function, associated with a significant increase in the populations of both early and late apoptotic cells (P < 0.05). However, treatment with 5 μM metformin (MET) under PA exposure significantly enhanced the viability of GCs and reduced the expression levels of pro-apoptotic BAX (P < 0.05). Next, we evaluated the effect of MET on cellular autophagy and found that MET treatment significantly downregulated the expression levels of phosphorylated mTORC1 (Ser2448), LC3B, and P62 while upregulating the expression levels of ULK1 in PA-treated GCs (P < 0.05). Our findings indicate that metformin improved palmitate-induced granulosa cell dysfunction by activating ULK1-mediated autophagy. Our findings will advance our understanding of reproductive dysfunction in obese ruminants, and provide a theoretical foundation for improving fertility in obese mammals.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2442-2452"},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216727","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":"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":"2259-2269"},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","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":"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":"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":"2137-2179"},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","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":"Identification and Validation of RPL7 and RCCD1 as Potential Biomarkers Associated with Immune Infiltration in Patients with Thin Endometrium.","authors":"Jiani Sun, Mei Ji, Yiping Zhu, Orhan Bukulmez, Yeung William Shu-Biu, Jing Sun, Xiaoming Teng, Miaoxin Chen","doi":"10.1007/s43032-025-01883-x","DOIUrl":"10.1007/s43032-025-01883-x","url":null,"abstract":"<p><p>Thin endometriumQuery (TE) significantly contributes to poor embryo implantation and female infertility, yet its pathogenesis remains unclear, limiting effective treatment options. To identify potential TE-associated genes and explore underlying mechanisms for clinical therapy, we conducted RNA sequencing on 18 TE and 18 normal endometrium samples, followed by bioinformatics analysis. Total RNA was extracted from samples, reverse-transcribed into cDNA, and sequenced on the HiSeq 2500 platform, followed by differential expression analysis and functional enrichment of differentially expressed genes (DEGs). Functional enrichment and LASSO analysis identified key biomarkers, which were subsequently validated at both mRNA and protein levels. Immune infiltration patterns and correlations with immune cells were also examined. Consequently, ribosomal protein L7 (RPL7) and RCC1 domain-containing 1 (RCCD1) were identified as potential biomarkers, showing overexpression in TE and association with abnormal immune regulation. These findings suggest that RPL7 and RCCD1 may serve as specific biomarkers for TE, providing insights that could aid in developing targeted therapeutics to improve clinical outcomes.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2202-2215"},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209343","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}