Feng Hao, Zhang Yan, Luo Shen, Wang Hui, Qiu Ling, Yang Xiaoyu, Jiang Hua
{"title":"Reverse-engineering the FLT3-PI3K/AKT axis to enhance TILs function and improve prognosis in ovarian and cervical cancers.","authors":"Feng Hao, Zhang Yan, Luo Shen, Wang Hui, Qiu Ling, Yang Xiaoyu, Jiang Hua","doi":"10.1186/s13048-025-01592-8","DOIUrl":"10.1186/s13048-025-01592-8","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancers (OC) and cervical cancers (CC) have poor survival rates. Tumor-infiltrating lymphocytes (TILs) play a pivotal role in prognosis, but shared immune mechanisms remain elusive.</p><p><strong>Methods: </strong>We integrated single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) to explore immune regulation in OC and CC, focusing on the PI3K/AKT pathway and FLT3 as key modulators. Seurat and Harmony were employed for batch correction and dimensionality reduction. FLT3 expression was mapped with spatial data from 10 × Genomics.</p><p><strong>Results: </strong>FLT3, identified as a regulator through the PI3K/AKT pathway, showed positive correlations with T cells, NK cells, and B cells. FLT3-high regions exhibited increased immune infiltration, particularly in CC, enhancing survival outcomes.</p><p><strong>Conclusion: </strong>This study provides the first spatially resolved evidence of FLT3's immune-modulatory role in OC and CC, positioning it as a promising immunotherapeutic target. FLT3-targeted strategies may offer new options for patients resistant to conventional therapies.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"14"},"PeriodicalIF":3.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039619","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}
Xiufen Zheng, Zikai Chen, Miao Liang, Liting Zhou, Miaoru Wang, Silin Zhang, Shuyun Zhang, Lei Ma, Wei Yi, Xiawen Liu
{"title":"Targeting UGT2B15 and NR1H4 interaction: a novel therapeutic strategy for polycystic ovary syndrome using naftopidil enantiomers.","authors":"Xiufen Zheng, Zikai Chen, Miao Liang, Liting Zhou, Miaoru Wang, Silin Zhang, Shuyun Zhang, Lei Ma, Wei Yi, Xiawen Liu","doi":"10.1186/s13048-025-01598-2","DOIUrl":"10.1186/s13048-025-01598-2","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder among women of reproductive age. It is characterized by hyperandrogenism, ovulatory dysfunction, and the presence of polycystic ovarian morphology (PCOM) on ultrasound, often accompanied by metabolic disturbances such as insulin resistance and obesity. Current treatments, including oral contraceptives and anti-androgen medications, often yield limited efficacy and undesirable side effects. This study investigates the role of UGT2B15, an essential enzyme for androgen metabolism, in PCOS pathogenesis and its potential as a therapeutic target.</p><p><strong>Methods: </strong>We used RNA sequencing to examine the effects of UGT2B15 knockdown in KGN cells. To modulate UGT2B15 expression, we employed siRNA and (R)/(S)-NAF (naftopidil), a chemical inducer of UGT2B15 identified in our previous studies on a prostate hyperplasia model. The effects of siRNA and (R)/(S)-NAF on dihydrotestosterone (DHT) levels, cell apoptosis, and the expression of apoptosis-related proteins in KGN cells were evaluated. In a PCOS mouse model, we assessed the effects of (R)-NAF and (S)-NAF on serum androgen levels, menstrual cycles, ovarian morphology, and UGT2Bs expression. Additionally, luciferase reporter and ChIP assays were utilized to study UGT2B15 regulation by NR1H4.</p><p><strong>Results: </strong>Elevated androgens were found to suppress UGT2B15 expression in ovarian granulosa cells, leading to DHT accumulation and apoptosis. (R)-NAF and (S)-NAF treatments reversed these effects, alleviating PCOS symptoms in mice such as hyperandrogenism, irregular menstrual cycles, and the presence of ovarian cysts. NR1H4 negatively regulated the transcription of UGT2B15 in KGN cells. (R)-NAF and (S)-NAF disrupted NR1H4 binding to the UGT2B15 promoter without affecting its protein levels, indicating direct interference with its regulation.</p><p><strong>Conclusions: </strong>UGT2B15 represents a promising target for novel PCOS therapies by modulating androgen metabolism and protecting ovarian granulosa cells from apoptosis. (R)-NAF and (S)-NAF regulate UGT2B15 by disrupting NR1H4's binding to its promoter, implying potential therapeutic compounds for PCOS treatment.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"13"},"PeriodicalIF":3.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059379","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":"Menopause mysteries: the exosome-inflammation connection.","authors":"Aarushi Sultania, Subhashini Brahadeeswaran, Aparna Eledath Kolasseri, Sivaraman Jayanthi, Ramasamy Tamizhselvi","doi":"10.1186/s13048-025-01591-9","DOIUrl":"10.1186/s13048-025-01591-9","url":null,"abstract":"<p><p>Extracellular vesicles, or exosomes, are produced by every type of cell and contain metabolites, proteins, lipids, and nucleic acids. Their role in health and disease is to influence different aspects of cell biology and to act as intermediaries between cells. Follicular fluid exosomes or extracellular vesicles (FF-EVs) secreted by ovarian granulosa cells are critical mediators of ovary growth and maturation. The movement and proteins of these exosomes are crucial in the regulation of cellular communication and the aging of cells, a process termed inflammaging. Menopause, a natural progression in the aging of females, is often accompanied by numerous negative symptoms and health issues. It can also act as a precursor to more severe health problems, including neurological, cardiovascular, and metabolic diseases, as well as gynecological cancers. Researchers have discovered pathways that reveal the diverse effects of exosome-driven cellular communication and oocyte development in the follicular fluid. It also explores the complex functions of FF exosomal proteins in the pathologies associated with menopause.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"12"},"PeriodicalIF":3.8,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029103","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}
Xuelan Li, Chujun Li, Jie Yang, Min Lin, Xianli Zhou, Ziyang Su, Yuting Zhang, Xinning Li, Xin Chen
{"title":"Associations of the levels of adipokines and cytokines in individual follicles with in vitro fertilization outcomes in women with different ovarian reserves.","authors":"Xuelan Li, Chujun Li, Jie Yang, Min Lin, Xianli Zhou, Ziyang Su, Yuting Zhang, Xinning Li, Xin Chen","doi":"10.1186/s13048-025-01594-6","DOIUrl":"10.1186/s13048-025-01594-6","url":null,"abstract":"<p><strong>Background: </strong>To a large extent, the ovarian reserve determines a woman's reproductive potential. The etiological and pathological mechanisms of diminished ovarian reserve (DOR) remain unclear, and no reliable treatment is currently available for DOR. Adipokines and cytokines in follicular fluid (FF) play pivotal roles in follicular development and maturation. The concentrations of adipokines and cytokines in FF from individual follicles of women with DOR undergoing in vitro fertilization (IVF) were studied. In particular, we investigated the associations between the levels of adipokines and cytokines in individual FFs from women with different ovarian reserves and between the follicular levels of adipokines and cytokines and IVF outcomes in individual follicles.</p><p><strong>Methods: </strong>A total of 115 women who underwent IVF were recruited. Patients diagnosed with DOR, defined as a basal antral follicle count < 5 or an anti-Mullerian hormone concentration < 1.1 ng/mL, were assigned to the DOR group, while patients with a normal ovarian reserve (NOR) were assigned to the NOR group. FF was sampled from the first follicle with a diameter of approximately 18-20 mm from each patient, and the IVF outcome of the oocyte from the corresponding follicle was tracked. The levels of 5 adipokines (including visfatin-1, monocyte chemoattractant protein-1 [MCP-1], resistin, leptin, and chemerin) and 3 cytokines (including interleukin [IL]-6, IL-12p70, and tumor necrosis factor [TNF]-α) in FF were determined by Luminex technology.</p><p><strong>Results: </strong>The follicular levels of TNF-α, IL-6, visafatin, MCP-1, IL-12, and chemerin were significantly lower in women with NOR than in those with DOR. The follicular level of IL-6 was negatively correlated with the quality of embryos according to the binary logistic regression analysis, while the follicular levels of adipokines and other cytokines did not correlate with IVF outcomes regardless of the woman's ovarian reserve.</p><p><strong>Conclusions: </strong>Our study demonstrated that the levels of adipokines and cytokines in individual follicles in women with DOR were different from those in women with NOR, indicating that increased intrafollicular inflammation might be related to DOR. Moreover, a high follicular level of IL-6 might negatively impact embryo quality.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"11"},"PeriodicalIF":3.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023746","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":"Study on the effects of Mogroside V in inhibiting NLRP3-mediated granulosa cell pyroptosis and insulin resistance to improve PCOS.","authors":"Wenqin Yang, Yujie Ma, Yafei Wu, Xiaocan Lei, Jing Zhang, Meixiang Li","doi":"10.1186/s13048-024-01563-5","DOIUrl":"10.1186/s13048-024-01563-5","url":null,"abstract":"<p><strong>Objective: </strong>Polycystic Ovary Syndrome (PCOS) is a prevalent endocrinopathy in reproductive-aged women, contributing to 75% of infertility cases due to ovulatory dysfunction. The condition poses significant health and psychological challenges, making the study of its pathogenesis and treatment a research priority. This study investigates the effects of Mogroside V (MV) on PCOS, focusing on its anti-inflammatory and anti-insulin resistance properties.</p><p><strong>Methods: </strong>Forty-five female Sprague-Dawley rats were divided into three groups: control, PCOS model, and MV treatment. The PCOS model was induced using a high-fat diet and letrozole. The MV treatment group was subsequently administered MV after the establishment of the PCOS model. The study monitored body mass, assessed estrous cycle changes, and measured serum hormone levels. Transcriptome sequencing and bioinformatics were used to identify differentially expressed genes related to inflammation and insulin resistance. Expression of pyroptosis and insulin resistance markers was analyzed using qRT-PCR, Western blot, and IHC. Additionally, an in vitro model assessed MV's impact on inflammation and insulin resistance.</p><p><strong>Results: </strong>The PCOS group exhibited elevated serum testosterone (T), luteinizing hormone (LH), insulin, and fasting glucose levels, along with increased insulin resistance (HOMA-IR) and decreased estradiol (E2), which were reversed by MV treatment. Transcriptome analysis identified significant gene expression changes between groups, particularly in pathways related to NLRP3 inflammation and insulin metabolism. MV treatment normalized the expression of ovarian pyroptosis factors (NLRP3, Caspase-1, GSDMD) and inflammatory cytokines (IL-1β, IL-18). In cellular models, MV increased E2 levels, reduced LDH release, and decreased the expression of insulin resistance and pyroptosis markers. Correlation analysis showed pyroptosis factors were positively correlated with HOMA-IR and IGF1, and negatively with IGF1R and E2 levels.</p><p><strong>Conclusion: </strong>MV improves PCOS by reducing pyroptosis and insulin resistance, enhancing insulin sensitivity, and promoting estrogen synthesis, thereby restoring granulosa cell function and follicular development.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"10"},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006897","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":"Effects of non-pharmacological interventions on biochemical hyperandrogenism in women with polycystic ovary syndrome: a systematic review and network meta-analysis.","authors":"Qi Jin, Ge Xu, Yuchen Ying, Lumin Liu, Huimin Zheng, Shifen Xu, Ping Yin, Yuelai Chen","doi":"10.1186/s13048-025-01595-5","DOIUrl":"10.1186/s13048-025-01595-5","url":null,"abstract":"<p><strong>Objective: </strong>To systematically evaluate the effectiveness of non-pharmacological interventions (NPIs), including electroacupuncture, exercise, diet, and lifestyle changes, in reducing androgen levels in women with polycystic ovary syndrome (PCOS) through a systematic review and network meta-analysis.</p><p><strong>Methods: </strong>Comprehensive searches were conducted in PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wanfang up to June 2024. Randomized controlled trials (RCTs) comparing NPIs with other NPIs or placebo treatments in adult women with PCOS were included. Study selection was independently performed by three authors. Quality assessment followed PRISMA guidelines using the Cochrane RoB2 tool. The confidence of evidence was examined using Confidence in Network Meta-Analysis (CINeMA). Traditional meta-analysis of continuous variables was conducted using Stata 17.0 software with a random-effects model, reporting effect sizes as standardized mean differences (SMD) and weighted mean differences (WMD). Network meta-analysis (NMA) was used to synthesize data, with network diagrams illustrating comparisons between NPIs. We assessed the consistency of the results, performed sensitivity analyses, and examined publication bias to evaluate the influence of individual studies. Furthermore, subgroup analysis and network meta-regression analysis were conducted to explore potential sources of heterogeneity.</p><p><strong>Results: </strong>The review included 21 studies with 1,196 participants, with meta-analysis focusing on 17 studies involving 1,013 participants. NPIs significantly reduced serum testosterone (SMD = -0.57; 95% CI: -0.86 to -0.29, p < 0.01), A4 (SMD = -1.37; 95% CI: -2.63 to -0.12, p = 0.03), and mFG score (WMD = -0.81; 95% CI: -1.26 to -0.37, p < 0.01). Notably, the reduction in testosterone levels achieved with NPIs met the Minimum Clinically Important Difference (MCID) of 12.47 ng/dL (WMD = -12.57; 95% CI: -18.92 to -6.23; p < 0.01), affirming the clinical relevance of these reductions. No significant effects were observed on Free Androgen Index (FAI), Sex Hormone-Binding Globulin (SHBG), Dehydroepiandrosterone (DHEA), DHEA Sulfate (DHEAS), Free Testosterone (FT), or Dihydrotestosterone (DHT) levels (all p > 0.05). The NMA (18 studies, 1,067 participants) identified electroacupuncture combined with diet and exercise as the most effective intervention for reducing serum testosterone (WMD = -21.75; 95% CI: -49.58 to 6.07; SUCRA 72.3%). Evidence certainty for many interventions was low, highlighting the need for higher-quality studies. Sensitivity analysis confirmed the robustness of the findings, and no publication bias was detected.</p><p><strong>Conclusions: </strong>NPIs, particularly electroacupuncture combined with exercise and dietary management, effectively reduce androgen levels in PCOS patients. These findings provide valuable guidance for clinicians and women with PCOS, with multi-component ap","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"8"},"PeriodicalIF":3.8,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006928","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}
Zhenye Zhu, Min Lei, Ruizhi Guo, Yining Xu, Yanqing Zhao, Chenlu Wei, Qingling Yang, Yingpu Sun
{"title":"Nicotinamide riboside supplementation ameliorates ovarian dysfunction in a PCOS mouse model.","authors":"Zhenye Zhu, Min Lei, Ruizhi Guo, Yining Xu, Yanqing Zhao, Chenlu Wei, Qingling Yang, Yingpu Sun","doi":"10.1186/s13048-025-01596-4","DOIUrl":"10.1186/s13048-025-01596-4","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility among women of reproductive age, yet the range of effective treatment options remains limited. Our previous study revealed that reduced levels of nicotinamide adenine dinucleotide (NAD<sup>+</sup>) in ovarian granulosa cells (GCs) of women with PCOS resulted in the accumulation of reactive oxygen species (ROS) and mitochondrial dysfunction. However, it is still uncertain whether increasing NAD<sup>+</sup> levels in the ovaries could improve ovarian function in PCOS. In this study, we demonstrated that supplementation with the NAD<sup>+</sup> precursor nicotinamide riboside (NR) prevented the decrease in ovarian NAD<sup>+</sup> levels, normalized estrous cycle irregularities, and enhanced ovulation potential in dehydroepiandrosterone (DHEA)-induced PCOS mice. Moreover, NR supplementation alleviated ovarian fibrosis and enhanced mitochondrial function in ovarian stromal cells of PCOS mice. Furthermore, NR supplementation improved oocyte quality in PCOS mice, as evidenced by reduced abnormal mitochondrial clustering, enhanced mitochondrial membrane potential, decreased ROS levels, reduced spindle abnormality rates, and increased early embryonic development potential in fertilized oocytes. These findings suggest that supplementing with NAD<sup>+</sup> precursors could be a promising therapeutic strategy for addressing ovarian infertility associated with PCOS.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"9"},"PeriodicalIF":3.8,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006881","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}
Haijuan Liu, Guohua Wang, Conglu Sui, Yanan Guo, Xiangyu He
{"title":"Woxuanzhongzhou formula improves DHEAS and high-fat diet-induced IR and anovulatory mice via AMPK/PGC1- α/Irisin pathway.","authors":"Haijuan Liu, Guohua Wang, Conglu Sui, Yanan Guo, Xiangyu He","doi":"10.1186/s13048-025-01587-5","DOIUrl":"10.1186/s13048-025-01587-5","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women of reproductive age. Anovulation is one of the most important clinical features of PCOS, and insulin resistance (IR) is one of the critical pathogenic factors. Woxuanzhongzhou (WXZZ) is a traditional herbal formulation that has shown efficacy in treating PCOS combined with IR, but the underlying mechanism is not clear. The aim of this study was to investigate the molecular mechanism of WXZZ on dehydroepiandrosterone sulfate and high fat diet induced PCOS with IR mice.</p><p><strong>Methods: </strong>40 female C57BL/6 mice were randomized to 4 groups: control group, model group, metformin group, and WXZZ group. Some mice is induced by dehydroepiandrosterone sulfate (DHEA) and high-fat diet (HFD) for 3 weeks. Following model induction, metformin and WXZZ were administered by gavage. Body weight, fasting blood glucose (FBG), fasting insulin (FINS) levels, the homeostatic model assessment of insulin resistance (HOMA-IR), and gonadal hormones were measured. Estrous cycles were monitored. The structure of the gastrocnemius muscle and subcutaneous fatty tissue were also evaluated. Additionally, serum irisin and non-esterified fatty acids (NEAF) levels and the protein and gene expression levels of AMPK, PGC1-α, FNDC5, irisin in the gastrocnemius muscle and CaMKK, AMPK, PGC1-α, UCP1 in fat were analyzed.</p><p><strong>Results: </strong>The DHEA + HFD + WXZZ group exhibited significant improvements in several key parameters compared to the DHEA + HFD group. WXZZ ameliorated endocrine and metabolic disorders, resumed estrous cycle in DHEAS and high-fat diet-induced IR and anovulatory mice. Significant reductions were observed in body weight, serum testosterone, luteinizing hormone, luteinizing hormone/ follicle-stimulating hormone ratio, FINS, and HOMA-IR. Additionally, WXZZ promoted irisin expression and secretion by up-regulating the protein and gene AMPK/PGC1-α/FNDC5 expression in gastrocnemius muscle and up-regulated the protein and gene CaMKK/AMPK/PGC1-α/UCP1 expression in fat. WXZZ inhibited the overproduction of serum NEFA, and reduced lipid accumulation. Structural analysis of the gastrocnemius muscle and adipose tissue revealed partial restoration.</p><p><strong>Conclusion: </strong>WXZZ exhibits therapeutic effects in DHEAS and high-fat diet-induced IR and anovulatory mice. These effects may be mediated through the activation of AMPK/PGC1-α pathway in muscle to promote the secretion of irisin.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"7"},"PeriodicalIF":3.8,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006901","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}
Lina He, Jie Lin, Zhengwen Qin, Qing Xu, Li Hao, Yanhong Fu, Xu Ran, Wei Chen
{"title":"Long non-coding RNA NEAT1 promotes ovarian granulosa cell proliferation and cell cycle progression via the miR-29a-3p/IGF1 axis.","authors":"Lina He, Jie Lin, Zhengwen Qin, Qing Xu, Li Hao, Yanhong Fu, Xu Ran, Wei Chen","doi":"10.1186/s13048-025-01588-4","DOIUrl":"10.1186/s13048-025-01588-4","url":null,"abstract":"<p><strong>Background: </strong>Granulosa cell proliferation and survival are essential for normal ovarian function and follicular development. Long non-coding RNAs (lncRNAs) have emerged as important regulators of cell proliferation and differentiation. Nuclear paraspeckle assembly transcript 1 (NEAT1) has been implicated in various cellular processes, but its role in granulosa cell function remains unclear.</p><p><strong>Methods: </strong>We investigated the function of lncRNA NEAT1 in human ovarian granulosa-like tumor cells (KGN). The effects of NEAT1 overexpression or silencing on cell proliferation and cell cycle were evaluated using CCK-8 assays and flow cytometry. The interaction between NEAT1, miR-29a-3p, and IGF1 was examined using dual-luciferase reporter assays, qRT-PCR, and Western blot analysis.</p><p><strong>Results: </strong>NEAT1 promoted granulosa cell proliferation and cell cycle progression by indirectly upregulated IGF1 expression through acting as a molecular sponge for miR-29a-3p. Cell proliferation and G2/M phase proportions were increased by overexpression of NEAT1, whereas cell proliferation and G2/M phase proportions decreased with NEAT1 silencing. The effects of NEAT1 on cell proliferation and cell cycle-related proteins (CCNB1 and CDK2) were partially reversed by miR-29a-3p mimic, while miR-29a-3p inhibitor rescued the effects of NEAT1 silencing.</p><p><strong>Conclusion: </strong>LncRNA NEAT1 could promote ovarian granulosa cell proliferation and cell cycle progression via the miR-29a-3p/IGF1 axis in polycystic ovary syndrome. Further investigation of this mechanism in clinical samples may have implications for understanding ovarian physiology and pathology.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"6"},"PeriodicalIF":3.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978993","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":"The effects of melatonin on follicular oxidative stress and art outcomes in women with diminished ovarian reserve: a randomized controlled trial.","authors":"Sonia Sadeghpour, Morteza Ghasemnejad-Berenji, Farzad Maleki, Tahereh Behroozi-Lak, Robabeh Bahadori, Hojat Ghasemnejad-Berenji","doi":"10.1186/s13048-024-01584-0","DOIUrl":"10.1186/s13048-024-01584-0","url":null,"abstract":"<p><strong>Background: </strong>To investigate the impact of Melatonin on follicular oxidative stress and assisted reproductive technology (ART) outcomes in women with diminished ovarian reserve (DOR).</p><p><strong>Method: </strong>We put 68 women with DOR who were going through ART into a randomized controlled trial. Starting on the fifth day of their menstrual cycle, we gave them either 3 mg of Melatonin or a placebo every day before stimulating their ovaries. We obtained follicular fluid during oocyte retrieval, assessed it for oxidative stress indicators, and documented ART outcomes.</p><p><strong>Results: </strong>Melatonin administration markedly enhanced the quantity of oocytes retrieved, fertilization rates, and embryo quality. In addition, Melatonin changed markers of oxidative stress, specifically the levels of reduced glutathione (rGSH) and total antioxidant capacity (TAC). The Melatonin group exhibited significantly elevated biochemical pregnancy rates.</p><p><strong>Conclusion: </strong>Melatonin may improve the quality of oocytes and help with reproductive technology in women with low ovarian reserves, possibly by lowering oxidative stress in the follicles.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"5"},"PeriodicalIF":3.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950483","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}