Journal of Ovarian Research最新文献

{"title":"Single-cell sequencing reveals PTX3 involvement in ovarian cancer metastasis.","authors":"Shuangyan Liu, Tianhao Wu, Xueying Song, Linru Quan, Xinyi Wang, Qing Liu, Xin Zhou","doi":"10.1186/s13048-024-01558-2","DOIUrl":"10.1186/s13048-024-01558-2","url":null,"abstract":"<p><strong>Background: </strong>Pentraxin 3 (PTX3) has been associated with the development and progression of various malignant tumors. However, its roles and the mechanisms underlying its involvement in ovarian cancer (OC) peritoneal metastasis remain unclear.</p><p><strong>Methods: </strong>Single-cell RNA sequencing (scRNA-seq) and immunohistochemistry (IHC) were conducted to determine the expression profiles, potential functionalities, and underlying mechanisms of PTX3 within the context of OC. To assess the proliferative response of OC cells, we utilized both EdU (5-ethynyl-2' -deoxyuridine) and CCK8 assays. The role of PTX3 in facilitating cell migration and invasion was quantified through the use of Transwell assays. The protein expression levels were meticulously analyzed via Western blotting. Furthermore, to explore the interactions between proteins, we conducted immunofluorescence (IF) staining and co-immunoprecipitation (Co-IP) experiments. To determine the factors responsible for the upregulation of PTX3, we performed both coculture and suspension assays, providing a comprehensive approach to understanding the regulatory mechanisms involved.</p><p><strong>Results: </strong>This study confirmed, for the first time, that the expression of PTX3 in OC metastatic lesions is greater than that in primary lesions and that tumor cells with high PTX3 expression have greater metastatic ability. PTX3 can activate the EMT and NF-κB signaling pathways in OC cells and can interact with the TLR4 and CD44 receptors in OC cells. Additionally, PTX3's modulation of the EMT and NF-κB pathways is partially dependent on its interaction with TLR4. Furthermore, this study revealed the intercellular regulatory network related to PTX3 in OC cells via bioinformatic analysis. High levels of PTX3 in OC cells potentially enhance the attraction of dendritic cells (DCs) and CD4 + T cells while diminishing the recruitment of B cells and CD8 + T cells. Finally, this study indicated that PTX3 upregulation was driven by multiple factors, including specific transcription factors (TFs) and modifications within the tumor microenvironment (TME).</p><p><strong>Conclusions: </strong>Our research revealed the contribution of PTX3 to the peritoneal dissemination process in OC patients, identifying a novel potential biomarker and therapeutic target for this disease.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"235"},"PeriodicalIF":3.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695501","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":"Unveiling the power of mitochondrial transfer in cancer progression: a perspective in ovarian cancer.","authors":"Caixia Wang, Chuan Xie","doi":"10.1186/s13048-024-01560-8","DOIUrl":"10.1186/s13048-024-01560-8","url":null,"abstract":"<p><p>Mitochondria are dynamic organelles integral to metabolic processes, coordination of essential biological pathways, and oncogenesis and tumor progression. Recent studies have revealed that mitochondria can be transferred between cells via multiple mechanisms, implicating their involvement in the pathogenesis and progression of ovarian cancer. This review provides a comprehensive analysis of intercellular mitochondrial transfer within the context of ovarian cancer and its tumor microenvironment. We also propose targeted pathways and therapeutic strategies that could be utilized to modulate diseases associated with mitochondrial transfer therapy. Finally, we examine recent advancements in this field and identify several unresolved questions.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"233"},"PeriodicalIF":3.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695518","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 predictive role of PD-L1 expression and CD8 + TIL levels in determining the neoadjuvant chemotherapy response in advanced ovarian cancer.","authors":"T Aliyeva, B Y Aktas, F Gundogdu, E Chalabiyev, Z Arik, A Usubutun","doi":"10.1186/s13048-024-01533-x","DOIUrl":"10.1186/s13048-024-01533-x","url":null,"abstract":"<p><strong>Objective: </strong>To analyze how the PD-L1 expression and CD8 + tumor infiltrating lymphocyte (TIL) levels in biopsy samples before neoadjuvant chemotherapy (NACT) can predict chemotherapy response score and survival for advanced high-grade serous ovarian cancer (HGSC).</p><p><strong>Methods: </strong>We retrospectively analyzed 45 patients with advanced epithelial ovarian cancer between 2010 and 2018, who had received at least three cycles of NACT. PD-L1 expression and CD8 + TIL levels were evaluated by immunohistochemical staining in the pre-NAC tumor samples from which the patients had been diagnosed. The post-NACT tissue samples taken during interval debulking surgery (IDS) were used to evaluate the chemotherapy response score (CRS).</p><p><strong>Results: </strong>Among all the patients, CRS 1 (no response) was found in 8 patients, CRS 2 (partial response) in 28 patients, and CRS 3 (complete response) in 9 patients. A total of 20 (44.4%) patients had high intratumoral CD8 + TILs (iCD8 + TILs) levels, and 35 (77.8%) patients had high expression stromal CD8 + TILs (sCD8 + TILs). No statistically significant relationship was found between high and low expression of i/s CD8 + TILs levels with PFS and CRS. The study found that 33 (73.3%) patients had high levels of stromal PD-L1 (sPD-L1) expression and 28 (62.2%) patients had high levels of intratumoral PD-L1 (iPD-L1) expression. In the iPD-L1 group, patients with low expression had a PFS of 28 months, whereas those with high expression had a PFS of 17 months (p = 0.028). Among the patients with high iPD-L1 expression, 23 (82.1%) patients showed CRS2, 4 (14.3%) showed CRS3, and only 1 (3.6%) showed CRS1 (p < 0.001). However, high or low expression sPD-L1 did not significantly affect PFS and CRS (p = 0.928 and p = 0.305; respectively).</p><p><strong>Conclusions: </strong>We found that iPD-L1 expression levels in diagnostic biopsy in ovarian cancer can predict the chemotherapy response score in interval debulking surgery.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"234"},"PeriodicalIF":3.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695508","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":"Gut microbiota and gut-derived metabolites are altered and associated with dietary intake in women with polycystic ovary syndrome.","authors":"Thaís Rasia da Silva, Lucas Bandeira Marchesan, Pabulo Henrique Rampelotto, Larisse Longo, Tiago Franco de Oliveira, Rikard Landberg, Vanessa de Mello, Poli Mara Spritzer","doi":"10.1186/s13048-024-01550-w","DOIUrl":"10.1186/s13048-024-01550-w","url":null,"abstract":"<p><strong>Background: </strong>Disturbances in the gut microbiota may act as mechanisms influencing the interplay between dietary factors and metabolic disorders. Studies have demonstrated that these alterations are associated with the diagnosis of polycystic ovary syndrome (PCOS). Within this context, we aimed to investigate associations between gut microbiota, gut-derived metabolites (short-chain fatty acids [SCFAs] and indole-3-propionic acid [IPA]), and dietary intake in women with PCOS.</p><p><strong>Methods: </strong>We conducted a cross-sectional study of 24 women with PCOS, previously recruited for two studies at our research center, compared with 14 age-matched healthy controls. The mean (SD) age of all 38 participants was 33.3 (7.5) years, and the mean (SD) body mass index was 29.5 (4.8) kg/m². Primary outcomes included gut microbiota analysis by sequencing the V4 region of the 16 S rRNA gene, serum IPA levels measured by liquid chromatography/triple-quadrupole mass spectrometry (LC-QqQ-MS), and fecal and plasma SCFA levels measured by LC-MS/MS.</p><p><strong>Results: </strong>Gut microbiota diversity, composition, and metabolic pathways differed between the PCOS and control groups. A higher abundance of two operational taxonomic units specializing in complex carbohydrate metabolism was observed in healthy control women. The PCOS group exhibited a less favorable dietary intake than the control group, and a significant correlation was observed between gut microbiota composition and dietary glycemic load in PCOS (r = 0.314, P = 0.03 in Mantel test). Multivariable-adjusted linear regression models indicated that lower levels of IPA and higher circulating levels of two SCFAs (acetic acid and propionic acid) were independently associated with the diagnosis of PCOS.</p><p><strong>Conclusions: </strong>Our data support the differentiation between women with PCOS and healthy controls based on gut microbiota analysis. Furthermore, changes in gut bacteria and their metabolites could be, at least in part, the biological mechanism by which a low glycemic load diet may potentially improve PCOS-related reproductive and cardiometabolic outcomes.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"232"},"PeriodicalIF":3.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693233","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":"Correction: Correlation between ovarian follicular development and Hippo pathway in polycystic ovary syndrome.","authors":"Zichao Huang, Tianyue Xu, Chunling Liu, Honghui Wu, Linglin Weng, Jieyu Cai, Na Liang, Hongshan Ge","doi":"10.1186/s13048-024-01557-3","DOIUrl":"10.1186/s13048-024-01557-3","url":null,"abstract":"","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"230"},"PeriodicalIF":3.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682110","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":"Characterization of the gut microbiota in patients with SARS-CoV-2 infection during controlled ovarian stimulation.","authors":"Tianjin Yang, Guanjian Li, Huayan Yin, Longmei Wu, Yunxia Cao, Bing Song","doi":"10.1186/s13048-024-01553-7","DOIUrl":"10.1186/s13048-024-01553-7","url":null,"abstract":"<p><strong>Background: </strong>The Coronavirus disease 2019 (COVID-19) pandemic has emerged as a global health crisis, with clinical manifestations including those suggesting injury to various organs such as the ovaries, which implies that it extends beyond respiratory infections. Changes in gut microbiota may exhibit correlations with the mechanisms and stages of severity in COVID-19, as well as a link with sex hormones, embryo development, and pregnancy. Controlled ovarian stimulation (COS) is used to induce the development of multiple high-quality follicles during in vitro fertilization (IVF). Our research aimed to investigate whether patients infected with COVID-19 have altered gut microbiota compositions that would affect the outcomes of COS.</p><p><strong>Methods: </strong>Twenty-one healthy females and seventeen patients with COVID-19 were enrolled. Samples were sequenced for gut microbiota identification through 16 S rRNA V3-V4 region, including species annotation, community diversity, and community functions.</p><p><strong>Results: </strong>No significant differences were found between the groups in terms of in IVF cycle outcomes and laboratory parameters. Patients with COVID-19 and healthy women showed no significant difference in the total number of available blastocyst embryos. Furthermore, the gut microbiota alpha diversity index in the COVID-19 group were markedly reduced compared to those of healthy females. Comparing the COVID-19 group to the controls, the gut microbiota dysbiosis decreased levels of Ruminococcus, and Agathobater, and elevated levels of Achromobacter and Raistonia. Finally, we identified a series of microbial functional characteristics, including membrane transport and carbohydrate metabolism, that exhibited significant disparities between the two groups.</p><p><strong>Conclusions: </strong>Patients in the COVID-19 group exhibited significant disparities in the gut microbiota composition compared to the healthy women during COS. However, the IVF outcomes did not show any significant differences between the two groups. Collectively, our speculation suggests that SARS-COV-2 infection may alter the gut microbiota without impacting IVF outcomes.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"231"},"PeriodicalIF":3.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682101","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":"Chiglitazar ameliorates dehydroepiandrosterone-induced polycystic ovary syndrome in rats.","authors":"Fuzhen Zhao, Wei Cui, Chengmei Fang, Yuanyuan Luo, Cheng Zhang","doi":"10.1186/s13048-024-01554-6","DOIUrl":"10.1186/s13048-024-01554-6","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder accompanied by ovulatory dysfunction. Insulin resistance (IR) is a key pathogenic mechanism in PCOS, and insulin sensitizers, such as metformin and pioglitazone, can improve PCOS symptoms. Chiglitazar, a pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist, is also an insulin sensitizer; however, its therapeutic effects have not yet been studied in PCOS. We evaluated the therapeutic effects of chiglitazar in a rat model of PCOS.</p><p><strong>Methods: </strong>Sprague-Dawley rats aged 4 weeks were injected subcutaneously with dehydroepiandrosterone (DHEA) (6 mg/100 g/day) to establish PCOS, and a control (CON) group was established. The rats were divided into the CON, PCOS model (DHEA), pioglitazone-treated (DHEA + PIO), and chiglitazar-treated (DHEA + CHI) groups. The DHEA + PIO group received pioglitazone (20 mg/kg/day) and the DHEA + CHI group received chiglitazar (20 mg/kg/day), each for 15 days. Body weight, estrous cycle, and glucose tolerance test (GTT) and insulin resistance test (ITT) results were monitored. Experimental animal energy metabolism systems were utilized to assess metabolic parameters. Enzyme-linked immunosorbent assay was conducted to detect changes in serum hormones, including insulin, adiponectin, sex-related hormones, and lipid metabolism indicators. The ovaries were used for molecular biology experiments to detect changes in Akt/phosphorylated Akt and glucose transporter 4 (GLUT4) expression by Western blotting and quantitative polymerase chain reaction.</p><p><strong>Results: </strong>Chiglitazar and pioglitazone improved PCOS symptoms. However, chiglitazar demonstrated a more pronounced effect on lipid improvement and weight gain than pioglitazone. In the DHEA + PIO and DHEA + CHI groups, there was notable recovery in oxygen consumption and carbon dioxide output; substantial improvement in GTT and ITT results; an increase in adiponectin; and a reduction in serum insulin, androgens, luteinizing hormone (LH), and LH/follicle-stimulating hormone ratio. Compared with the DHEA group, the DHEA + CHI group exhibited notable decreases in triglycerides, free fatty acids, and atherosclerosis index, while the DHEA + PIO group demonstrated no changes. Granulosa cells and healthy follicles increased in ovarian sections. Ovarian steroidogenic enzymes also increased in the DHEA + PIO and DHEA + CHI groups compared with the DHEA group. Mechanistically, chiglitazar increased Akt phosphorylation.</p><p><strong>Conclusion: </strong>Chiglitazar significantly improved ovulation in rats with PCOS and may be a potential novel therapeutic strategy for PCOS.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"229"},"PeriodicalIF":3.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676099","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 dietary phytochemical index and its relation to polycystic ovary syndrome: a case-control study.","authors":"Yasong Chi, Ruiqin Yue, Yanru Lv, Haiyan Li, Wei Liao","doi":"10.1186/s13048-024-01540-y","DOIUrl":"10.1186/s13048-024-01540-y","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS), a hormonal disorder affecting women of reproductive age, can be significantly impacted by diet. This study explores the relationship between a diet rich in phytochemicals, measured by the Dietary Phytochemical Index (DPI), and PCOS, along with associated health markers.</p><p><strong>Methods: </strong>A case-control study design was implemented with 480 individuals diagnosed with PCOS based on the Rotterdam criteria, paired with 480 controls matched in terms of age and BMI. The evaluation encompassed dietary intake, anthropometric measurements, and hormonal/metabolic markers. Additionally, the DPI score was determined based on the consumption of phytochemical-rich foods. The study also examined PCOS-related complications like acne and irregular menstrual cycles, as well as mental health using the Beck Depression Inventory (BDI-II) scores.</p><p><strong>Results: </strong>Women with PCOS had significantly lower DPI scores (32.42 vs 43.87, p < 0.001) compared to the control group, indicating a less phytochemical-rich diet. The DPI scores coincided with higher levels of hormones typically associated with PCOS, including Luteinizing Hormone (LH), Dehydroepiandrosterone Sulfate (DHEA-S), and testosterone. Additionally, these scores were associated with markers of metabolic dysfunction such as C-reactive Protein (CRP), Fasting Blood Sugar (FBS), and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), while positively correlating with Sex Hormone-Binding Globulin (SHBG) (all p < 0.050).). Higher DPI scores were associated with a significantly reduced risk of PCOS (OR: 0.13, 95% CI: 0.08, 0.23, P for trend: 0.001) and its complications, including acne and irregular menstrual cycles. Interestingly, a positive association emerged, suggesting better mental health (lower BDI-II scores) with higher DPI scores.</p><p><strong>Conclusions: </strong>In conclusion, this study indicates that lower DPI scores are associated with a higher incidence and severity of PCOS, suggesting that a phytochemical-rich diet could potentially benefit the management of PCOS by enhancing hormonal profiles, metabolic health, and mental well-being in women.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"228"},"PeriodicalIF":3.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644469","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":"Correction: Transcriptomics of cumulus cells - a window into oocyte maturation in humans.","authors":"Brandon A Wyse, Noga Fuchs Weizman, Seth Kadish, Hanna Balakier, Mugundhine Sangaralingam, Clifford L Librach","doi":"10.1186/s13048-024-01529-7","DOIUrl":"10.1186/s13048-024-01529-7","url":null,"abstract":"","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"227"},"PeriodicalIF":3.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644467","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":"Human umbilical cord mesenchymal stem cell-derived extracellular vesicles harboring IGF-1 improve ovarian function of mice with premature ovarian insufficiency through the Nrf2/HO-1 pathway.","authors":"Hui Miao, Congxiu Miao, Na Li, Jing Han","doi":"10.1186/s13048-024-01536-8","DOIUrl":"10.1186/s13048-024-01536-8","url":null,"abstract":"<p><strong>Objective: </strong>Premature ovarian insufficiency (POI) is a disease with medical, psychological and reproductive implications, but its common therapies have limited efficacy and a likelihood of complications. This study delves into the therapeutic role of human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUC-MSCs-EVs) in POI mice through the insulin-like growth factor 1 (IGF-1)/nuclear factor E2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/autophagy pathway.</p><p><strong>Methods: </strong>hUC-MSCs were transfected with lentiviral short hairpin RNA of IGF-1 before EV extraction. Cyclophosphamide (CTX)-induced POI mouse models were administrated with hUC-MSCs-EVs. Mouse ovarian granulosa cells (GCs) were induced with CTX, then treated with hUC-MSCs-EVs and ML385. Ovarian histopathological changes were observed, changes in follicle number at all levels were counted and serum sex hormones were evaluated, as well as LC3II/I and Beclin-1 expression. GCs were subject to detection of proliferation, deaths, oxidative stress, and Nrf2 nuclear translocation.</p><p><strong>Results: </strong>After CTX exposure, mice showed thinner GCs layer in the ovary, reduced number of GCs and follicles at all levels, disturbed serum sex hormones, enhanced oxidative stress and autophagy, and downregulated ovarian IGF-1; whereas, hUC-MSCs-EVs upregulated IGF-1 to improve the ovarian function. hUC-MSCs-EVs carrying IGF-1 activated Nrf2/HO-1 signaling to inhibit CTX-induced excessive autophagy of GCs, but this ameliorative effect was partially weakened by inhibiting Nrf2/HO-1 signaling. hUC-MSCs-EVs inhibited excessive autophagy of GCs and improved ovarian function of CTX-induced mice through IGF-1/Nrf2/HO-1 pathway.</p><p><strong>Conclusion: </strong>hUC-MSCs-EVs activate the Nrf2/HO-1 signaling by carrying IGF-1, which in turn inhibits excessive autophagy and damage of GCs, thus improving ovarian function in POI mice.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"224"},"PeriodicalIF":3.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622445","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}