{"title":"The Role of the Microbiome in Endometriosis.","authors":"Sabri Saeed Sanabani","doi":"10.1007/s43032-025-01985-6","DOIUrl":"https://doi.org/10.1007/s43032-025-01985-6","url":null,"abstract":"<p><p>Endometriosis is a chronic gynecological disease characterized by the presence of endometrial-like tissue outside the uterus, leading to pain and infertility. Recent research has highlighted the important role of the microbiome in various health conditions, including endometriosis. The aim of this review is to examine the central role of the microbiome in the development and treatment of endometriosis. Key findings include the influence of the gut microbiota on estrogen metabolism, whereby certain bacteria can increase estrogen levels and systemic inflammation and exacerbate endometriosis. Changes in the vaginal and endometrial microbiota are also associated with the disease, as they influence inflammatory and estrogen-dependent metabolic pathways. Dysbiosis in various microbiomes can affect inflammatory pathways, with a shift in the vaginal microbiota to the upper reproductive tract affecting endometriosis without symptoms. Probiotic interventions show promise in restoring a healthy microbiota and improving outcomes, with clinical trials demonstrating the efficacy of lactobacilli-based medications for pain relief. In addition, diet and lifestyle changes can directly impact the gastrointestinal microbiome, reducing inflammation and potentially influencing endometriosis. Future research should focus on establishing comprehensive microbiome profiles, mechanistic studies and longitudinal studies to discover new therapeutic targets and improve clinical outcomes for women with endometriosis.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280939","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":"HERC2 as a Potential Biomarker for Prognosis and Response to Bevacizumab in Ovarian Cancer: A Bioinformatics Approach.","authors":"Fatih Yay, Hasan Çağrı Yıldırım","doi":"10.1007/s43032-025-01977-6","DOIUrl":"https://doi.org/10.1007/s43032-025-01977-6","url":null,"abstract":"<p><p>It is thought that decreased HERC2 expression increases the sensitivity to ferroptosis in ovarian cancer cells and may increase the VEGF pathway in porcine endothelium by inhibiting LKB1. Based on these data, we aimed to determine whether HERC2 expression may have a positive prognostic significance in patients receiving anti-VEGF based therapy in ovarian cancer patients. The study used public databases and has a retrospective design. Following web tools or datasets were used: TCGA TARGET GTEX study (n = 427 cancer vs. 88 normal ovarian tissue) at UCSC Xena and CPTAC at UALCAN for expression, Kaplan-Meier plotter for overall survival (OS) (n = 1207 for serous histology and n = 37 for endometrioid histology in gene chip), progression-free survival (PFS) (n = 1104 for serous histology in gene chip), TIMER2.0 for correlation of PDCD1, CTLA4, CD274 (PDL1), GEPIA2 for immune gene signatures, OncoLnc, DoSurvive and OncomiR for miRNA and OS associations, CancerSEA for functional status analyses. HERC2 expression levels were lower in ovarian serous cystadenocarcinoma (OV). Lower HERC2 expression was also seen in CPTAC ovarian cancer cohort. In the overall ovarian cancer cohort, decreased HERC2 expression was associated with longer OS. In the serous histology cohort, decreased HERC2 expression was associated with shorter PFS in those receiving bevacizumab-containing chemotherapy. PDL1 and HERC2 expressions were positively correlated. hsa-miR-500a-3p was negatively correlated with HERC2 in OV, and increased expression of this miRNA was associated with better OS. There was a positive association between HERC2 expression and angiogenesis and EMT, and a negative association with invasion. Decreased HERC2 expression is associated with a favorable prognosis in overall ovarian cancer cohort, but is associated with a worse PFS in patients receiving bevacizumab with serous ovarian cancer.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281006","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}
Meiting Qiu, Junjie Qu, Jingyun Wang, Yunqing Zhi, Xiaoming Teng
{"title":"The Methylation Regulator PRDM6 Confers Protection Against Polycystic Ovary Syndrome: Evidences from Bioinformatics and Experimental Approaches.","authors":"Meiting Qiu, Junjie Qu, Jingyun Wang, Yunqing Zhi, Xiaoming Teng","doi":"10.1007/s43032-025-01994-5","DOIUrl":"https://doi.org/10.1007/s43032-025-01994-5","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with an unclear epigenetic basis. This study sought to identify critical methylation regulators implicated in PCOS progression and evaluate their therapeutic potential through comprehensive experimental validation. Bioinformatics analysis was performed to screen differentially expressed genes (DEGs) associated with PCOS and methylation regulators from public databases. Intersection analysis revealed PRDM6 as a key methylation regulator among 177 PCOS-related DEGs and 175 known methylation regulators. Further in silico prediction identified 16 PRDM6-correlated DEGs harboring potential post-translational modification (PTM) sites, with functional enrichment analysis linking them to the cAMP signaling pathway, notably involving RAC3, FXYD1, and SSTR2. To validate these findings, we established in vivo PCOS models using dehydroepiandrosterone-induced rats and in vitro models to mimic PCOS-associated insulin resistance using insulin-induced granulosa cells. In the rodent model, PRDM6 expression was significantly downregulated, while lentivirus-mediated PRDM6 overexpression restored serum sex hormone levels (measured by ELISA) and ameliorated ovarian histopathological abnormalities (assessed via hematoxylin-eosin staining). In vitro, PRDM6 upregulation in granulosa cells attenuated insulin-induced hyperproliferation (evaluated by CCK-8 and EdU assays) and suppressed pro-inflammatory responses (quantified by ELISA). Collectively, these results demonstrated that PRDM6 serves as a pivotal methylation regulator in PCOS pathogenesis, with therapeutic relevance in mitigating hormonal dysregulation, ovarian dysfunction, aberrant granulosa cell proliferation, and inflammation. This study provides novel insights into the epigenetic mechanisms underlying PCOS and highlights PRDM6 as a potential therapeutic target.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239290","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":"Differential Methylation Signatures Associated with PCOS- A Systematic Review and In-Silico Analysis.","authors":"Priya Sharma, Ahelee Ghosal, Aiswarya Vs, Shweta Daryani, Tulsi Brahma, Preeti Khetarpal","doi":"10.1007/s43032-025-01976-7","DOIUrl":"https://doi.org/10.1007/s43032-025-01976-7","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a common endocrinopathy affecting 5-20% of reproductive-age women. Besides genetic factors, environmental triggers are considered major underlying causes that play a role through epigenetic alterations. Since epigenetic studies can be a possible link to explain the complexity of multifactorial disorders, it is worthwhile to investigate differentially methylated regions (DMRs) associated with PCOS. Therefore, a systematic review was conducted to identify epigenetic modifications associated with PCOS and analyse their functional role in the pathogenesis of the syndrome. After following inclusion and exclusion criteria, various databases (PubMed, Google Scholar, Central Cochrane Library, and Science Direct) were searched with predetermined keywords up to 30th June 2025, and quality of the selected articles assessed through the Newcastle Ottawa scale (NOS). In-silico analysis was performed by STRING, and Shiny GO. A total of 46 eligible studies were included, were further sub-categorized based on the sample type. A total of one hundred eleven genes were identified with altered DMRs, out of which thirty seven genes were reported from the ovarian tissues alone. Their GO analysis shows a significant interaction with other PCOS-susceptible genes and their functions in female sex differentiation and gonadal development. However, in-silico analysis of thirty six genes identified in blood showed their functions were significantly involved in the insulin-like growth factor binding activity. Gene enrichment analysis of fifteen genes with altered methylation identified in adipose tissue shows the significant involvement of female sex differentiation and insulin-activated receptor functions. Further, alterations in methylation of which genes (INSR, AMHR2, YAP1, CYP19A1, LHCGR, CDKN1A, LINE-1, AMH and TOX3) have been reported by at least two separate studies, irrespective of sample type. Their in-silico analysis shows significant involvement of these genes in the female sex characters, and gonadal development The current study highlights tissue-specific epigenetic modifications in PCOS, summarizes DMRs of genes which are involved in reproductive and insulin-related pathways. DMRs of identified genes may have a role in the pathogenesis of PCOS, insight into which may provide novel therapeutic targets in the future.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233273","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":"How Many Blastocysts Are Needed for PGT-A to Benefit RPL Patients? A 7-Year Retrospective Cohort Study.","authors":"Jia Liao, Shiheng Zhu, Jinghan Wang, Xinyi Xue, Chunzi Lyu, Qian Zhang, Junhao Yan, Tianxiang Ni","doi":"10.1007/s43032-025-01978-5","DOIUrl":"https://doi.org/10.1007/s43032-025-01978-5","url":null,"abstract":"<p><p>The efficacy of preimplantation genetic testing for aneuploidy (PGT-A) in couples with unexplained recurrent pregnancy loss (uRPL) may vary according to the number of good-quality blastocysts available. This study is to determine whether PGT-A could improve the cumulative live birth rate (CLBR) among couples experiencing uRPL as the number of high-quality blastocysts increases. A retrospective study involving 1073 couples with uRPL was conducted at a university-affiliated reproductive center. Patients were divided into two groups: 813 participants who underwent PGT-A and 260 participants who underwent conventional in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). A stratified analysis was conducted, which categorized the female participants into three subgroups based on the number of high-quality blastocysts: 1-3, 4-6, and ≥ 7. A binary logistic regression model was used to evaluate the associations between the number of high-quality blastocysts and the cumulative pregnancy outcomes. Among uRPL patients undergoing PGT-A or IVF/ICSI, there were respectively 421 vs. 129 with 1-3 blastocysts, 252 vs. 69 with 4-6 blastocysts, and 140 vs. 62 with ≥ 7 blastocysts. In 1-3 blastocysts subgroup, CLBR was 23.52% after PGT-A vs. 33.33% after IVF/ICSI (adjusted OR 1.005, 95% CI 0.604-1.674, p = 0.984). In 4-6 blastocysts subgroup, CLBR was 53.17% after PGT-A vs. 75.36% after IVF/ICSI (adjusted OR 0.398, 95% CI 0.197-0.802, p = 0.010). In ≥ 7 blastocysts subgroup, CLBR was 73.57% after PGT-A vs. 66.13% after IVF/ICSI (adjusted OR 1.660, 95% CI 0.729-3.799, p = 0.227). In these three subgroups, clinical pregnancy loss rates were all similar between the two treatment methods. In women with uRPL, PGT-A did not improve CLBR, irrespective of the number of high-quality blastocysts available. Routine use of PGT-A in this population is therefore not recommended. Future high-quality randomized controlled trials may better define its appropriate indications.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213658","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":"Polycystic Ovary Syndrome: Unraveling the Minor Shifts in Fatty Acid Composition of Follicular Fluid Phospholipids and Triglycerides.","authors":"Reza Zarezadeh, Amir Fattahi, Laya Farzadi","doi":"10.1007/s43032-025-01992-7","DOIUrl":"https://doi.org/10.1007/s43032-025-01992-7","url":null,"abstract":"<p><p>The effect of polycystic ovary syndrome (PCOS) on the fatty acid (FA) content of follicular fluid (FF) is not fully understood. The present study aimed to determine whether the FA composition of FF phospholipids (PLs) and triglycerides (TGs) undergoes alterations in women with PCOS. A total of 40 subjects, including 20 PCOS patients and 20 controls, were enrolled. Thin-layer chromatography followed by gas chromatography was carried out to isolate FF lipid fractions and measure relative concentrations of their FAs, respectively. Percentages of individual FAs in FF PLs and TGs did not statistically differ between the control and PCOS groups (p > 0.05), other than palmitoleic acid, which significantly decreased and increased in PLs and TGs of women with PCOS, respectively (p < 0.05). There were positive correlations between intrafollicular levels of androgens and PL levels of several n-6 polyunsaturated FAs in the PCOS group (r > 0.4, p < 0.05). In addition, relative concentrations of eicosapentaenoic acid in both PL and TG fractions were inversely correlated with the fertilization rate (r < -0.4, p < 0.05). PCOS women with positive pregnancy outcomes also had higher PL and TG stearic acid with concomitant lower docosahexaenoic acid and peroxidizability index in PL and TG fractions, respectively (p < 0.05). It could be concluded that PCOS was associated with minor alterations in the FA composition of FF PLs and TGs. Furthermore, there were differential fraction-dependent associations between FF FA profile and biochemical and reproductive parameters in women with PCOS.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213666","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}
Marie Maruyama, Takeshi Nagamatsu, Satoko Kawauchi, Izumi Nishidate, Shunichi Sato
{"title":"Optical Monitoring of the Therapeutic Effects of Resveratrol on Neonatal Hypoxic-Ischemic Encephalopathy Using Diffuse Reflectance Spectroscopy.","authors":"Marie Maruyama, Takeshi Nagamatsu, Satoko Kawauchi, Izumi Nishidate, Shunichi Sato","doi":"10.1007/s43032-025-01975-8","DOIUrl":"https://doi.org/10.1007/s43032-025-01975-8","url":null,"abstract":"<p><p>Hypoxic-ischemic encephalopathy (HIE), which precipitates during parturition, causes severe neurological sequelae in the neonate. We have previously reported an optical monitoring system based on diffuse reflectance spectroscopy to evaluate brain tissue damage that precedes HIE. This study aimed to evaluate the effects of resveratrol on the suppression of HIE development using this monitoring system. After left carotid artery ligation, neonatal rats were intraperitoneally injected with 20 or 40 mg/kg resveratrol and subjected to hypoxic stress. HIE lesions were assessed after 24 h using triphenyl tetrazolium chloride staining. HIE developed in the non-treated group and the group treated with 20 mg/kg administration. Optical parameter assessment during hypoxic stress revealed that HIE-induced brain damage was characterized by a decrease in scatter amplitude, an increase in total hemoglobin in the cerebral blood flow, and a reduction in tissue oxygen saturation. HIE development was completely suppressed in the 40 mg/kg group, in which the changes in the optical parameters were also suppressed. These findings suggest that resveratrol exerts protective effects against HIE by enhancing oxygen supply to the brain. Resveratrol administration could be a promising approach for preventing neonatal HIE.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149901","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":"Regional Proteomic Characterization of Uterine Leiomyomas: Implications for Molecular Pathways and Tumor Biology.","authors":"Mustafa Gani Sürmen, Enis Özkaya","doi":"10.1007/s43032-025-01969-6","DOIUrl":"https://doi.org/10.1007/s43032-025-01969-6","url":null,"abstract":"<p><p>Uterine leiomyomas are the most common benign smooth muscle tumors in women of reproductive age. Recent technological advances have enhanced the potential of proteomic studies to identify proteins and related signaling pathways involved in leiomyoma pathogenesis. This study performed comprehensive proteomic analyses of three leiomyoma subtypes, classified by their localizations, to provide new insights and a valuable resource for further studies. Tissue samples from both leiomyoma and normal myometrial tissues were collected from individuals undergoing hysterectomy for symptomatic leiomyomas. Proteins were extracted from tissue samples, enzymatically digested to generate peptides, and subsequently analyzed using high-resolution mass spectrometry (HR-MS). Biological significance and related pathways of differentially expressed proteins were revealed by Gene Ontology (GO) analyses. MS analyses revealed significant expression changes in 143, 152 and 146 proteins in submucosal, subserosal and intramural myomas, respectively. Top enriched categories of dysregulated proteins included RNA binding, oxidoreductase activity, cytoskeletal structural components, glutathione transferase activity, extracellular matrix organization, innate immunity, post-translational phosphorylation. The classification of differentially expressed proteins (DEPs) also highlighted the metabolite interconversion enzyme family in all three groups. Hydrolase, oxidoreductase and transferase subfamilies were common to all three groups, while isomerase, ligase and lyase subfamilies were present in the subserosal and intramural groups. Proteomic analyses provided important information about the dysregulated proteins in uterine leiomyomas and revealed various pathways to which they are related. The findings emphasize the need for further research, especially on the effects of oxidative stress on the immune response against tumor cells, the role of extracellular matrix proteins and enzymes in metabolic pathways.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086154","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 Role of PRMT5 in Embryonic Developmental Arrest: Insights from IVF-ET Discarded Human Embryos.","authors":"Ningyu Sun, Shifeng Li, Kai Li, Ping Yin, Xiufang Zhong, Yuanyuan Chen, Lu Lu, Yun Li, Yuanyuan Wu, Hua Yan, Wuwen Zhang","doi":"10.1007/s43032-025-01957-w","DOIUrl":"https://doi.org/10.1007/s43032-025-01957-w","url":null,"abstract":"<p><p>Embryonic developmental arrest is a critical factor affecting the success rate of in vitro fertilization and embryo transfer (IVF-ET), and protein arginine methyltransferase 5 (PRMT5) plays a crucial role in early embryonic development. However, the mechanisms by which PRMT5 regulates embryonic development remain largely unexplored. Following the acquisition of informed consent from the patients, human embryos discarded from the IVF process were collected as experimental material. Real-time quantitative polymerase chain reaction (qRT-PCR) and confocal analysis were employed to quantify the levels of PRMT5 mRNA and protein at different developmental stages of early embryos, as well as to assess changes in H4R3me2s methylation levels. Furthermore, PRMT5 knockdown was performed in developmentally arrested embryos to observe its impact on further embryonic development. The results demonstrated a significant increase in both PRMT5 mRNA and protein levels in arrested embryos compared to control embryos. Additionally, a significant increase in the methylation level of H4R3me2s was observed in arrested embryos. The knockdown of PRMT5 has the potential to rescue some of the developmentally arrested embryos. In conclusion, the results of this study indicate that overexpression of PRMT5 leads to developmental arrest in early embryos, which can be partially rescued by knocking down the PRMT5 protein.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086233","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}