Idrees A Shah, Rabiya Rashid, Haroon Rashid, Abid Bhat, Mohd Ashraf Ganie
{"title":"Association of TCF7L2 genetic variants rs12255372 and rs7903146 with the polycystic ovary syndrome risk: systemic review and meta-analysis.","authors":"Idrees A Shah, Rabiya Rashid, Haroon Rashid, Abid Bhat, Mohd Ashraf Ganie","doi":"10.1186/s13048-024-01585-z","DOIUrl":"https://doi.org/10.1186/s13048-024-01585-z","url":null,"abstract":"<p><strong>Background: </strong>A significant overlap in the pathophysiological features of polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus (T2DM) has been reported; and insulin resistance is considered a central driver in both. The expression and hepatic clearance of insulin and subsequent glucose homeostasis are mediated by TCF7L2 via Wnt signaling. Studies have persistently associated TCF7L2 genetic variations with T2DM, however, its results on PCOS are sparse and inconsistent.</p><p><strong>Methods: </strong>We performed a comprehensive literature review of the data published till June 2024, on rs7903146, rs12255372, and PCOS in PubMed, Medline, the Cochrane Library, Google Scholar, Science Direct, Scopus, and Web of Science, followed by a meta-analysis to evaluate the association between these genetic variations and the PCOS risk. Using a random effects model, the pooled odds ratio (OR) and confidence intervals (95%CI) were computed using STATA statistical software.</p><p><strong>Results: </strong>The genotypic data from 3052 controls and 2291 women with PCOS from ten published studies were analysed. The results indicated no cumulative association between the rs7903146 variant and PCOS risk in either the allelic (C vs. T: OR = 1.21; 95% CI: 0.96-1.47, p > 0.05) or genotypic models (CC vs. CT + TT: OR = 1.06; 95% CI: 0.90-1.23, p > 0.05). Similarly, the genetic variant rs12255372 was not associated with PCOS risk both in the allelic and the dominant inheritance model(p > 0.05). Unlike East Asians (MAF < 0.025), both variants are highly frequent across other global populations including America, South Asia, and Europe (MAF ≥ 0.19).</p><p><strong>Conclusion: </strong>Unlike T2DM, our results showed that rs7903146 and rs12255372 variants of the TCF7L2 gene do not modulate the PCOS risk. However, the role of other TCF7L2 variants remains to be studied in future studies.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"2"},"PeriodicalIF":3.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11702189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029105","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":"Development of machine learning models for diagnostic biomarker identification and immune cell infiltration analysis in PCOS.","authors":"Wenxiu Chen, Jianliang Miao, Jingfei Chen, Jianlin Chen","doi":"10.1186/s13048-024-01583-1","DOIUrl":"10.1186/s13048-024-01583-1","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age. It is characterized by symptoms such as hyperandrogenemia, oligo or anovulation and polycystic ovarian, significantly impacting quality of life. However, the practical implementation of machine learning (ML) in PCOS diagnosis is hindered by the limitations related to data size and algorithmic models. To address this research gap, we have increased the sample size in our study and aim to utilize two ML algorithms to analyze and validate diagnostic biomarkers, as well as explore immune cell infiltration patterns in PCOS.</p><p><strong>Methods: </strong>We performed RNA-seq analysis on granulosa cell, including 13 samples from normal controls and 25 samples from women with PCOS. The data from our study were combined with publicly available databases. Batch effects were corrected using the 'sva' package in R software. Differential expression analysis was performed to identify genes that exhibited significant differences between the two groups. These differentially expressed genes (DEGs) were further analyzed for Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Hub genes were selected by intersecting the results of both methods after using LASSO and SVM-RFE for central gene selection for DEGs. Receiver Operating Characteristic (ROC) curves were employed to verify the accuracy of models by SVM and XGBoost. CIBERSORT analysis was performed to determine the relative abundances of immune cell populations. GSEA was analyzed to illustrate the expression patterns of genes within highly enriched functional pathways. RT-qPCR was used to validate the reliability of hub genes.</p><p><strong>Results: </strong>824 DEGs were found between the normal control and PCOS groups, including 376 upregulated and 448 downregulated genes. These DEGs were associated with endocytosis, salmonella infection and focal adhesion based on the KEGG enrichment analysis. Through overlapping LASSO and SVM-RFE algorithms, we identified four hub genes (CNTN2, CASR, CACNB3, MFAP2) that are significantly associated with the PCOS group. The diagnostic efficacy validation set using SVM and XGBoost yielded AUC values of 0.795 and 0.875, respectively, indicating their potential as diagnostic biomarkers. Consistent with the data analysis, the upregulation of CNTN2, CASR, CACNB3, and MFAP2 in PCOS was confirmed by RT-qPCR analysis on human granulosa cells. Furthermore, according to CIBERSORT analysis, a significant reduction in CD4 memory resting T cells was revealed in the PCOS group compared to the normal control group (P < 0.05).</p><p><strong>Conclusions: </strong>This study identified CNTN2, CASR, CACNB3, and MFAP2 as potential diagnostic biomarkers for PCOS, which provides strong evidence for existing research on hub genes. Furthermore, the analysis of immune cell infiltration revealed the significant involvement of CD4 memo","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927149","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":"Mechanisms of He Shi Yu Lin formula in treating premature ovarian insufficiency: insights from network pharmacology and animal experiments.","authors":"Yun Huang, Qin Zhang, Dan Shen, Xi Bao","doi":"10.1186/s13048-024-01575-1","DOIUrl":"10.1186/s13048-024-01575-1","url":null,"abstract":"<p><strong>Objective: </strong>He Shi Yu Lin Formula (HSYLF) is a clinically proven prescription for treating premature ovarian insufficiency (POI), and has shown a good curative effect. However, its molecular mechanisms are unclear. This study aimed to investigate the molecular mechanisms of HSYLF and clarify how network pharmacology analysis guides the design of animal experiments, including the selection of effective treatment doses and key targets, to ensure the relevance of the experimental results.</p><p><strong>Methods: </strong>Network pharmacology, molecular docking, and animal experiments were utilized to investigate the effects of HSYLF. Key targets were identified by intersecting herb and disease targets to construct protein-protein interaction and \"active components-intersection targets-disease\" networks. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed using the clusterProfiler package in R. A total of 50 specific pathogen-free female mice of reproductive age were included in the animal experiments. They were divided into five groups: the positive control group, the high-dose HSYLF group, the low-dose HSYLF group, the model blank group, and the normal control group, to evaluate the serum anti-müllerian hormone levels, mitochondrial morphology in oocytes, the levels of reactive oxygen species (ROS), and mitochondrial membrane potential.</p><p><strong>Results: </strong>Network pharmacology identified 204 active components connecting 219 key therapeutic targets for POI. Gene Ontology enrichment analysis indicated that the anti-POI targets of HSYLF mainly regulated response to xenobiotic stimulus, cellular response to chemical stress, and response to oxidative stress; and the Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested the primary pathways, including lipid and atherosclerosis, advanced glycation end product-receptor for advanced glycation end product signaling pathway in diabetic complications, bladder cancer, tumor necrosis factor signaling pathway, and interleukin-17 signaling pathway. The low-dose (33 g/kg/d) HSYLF and high-dose (66 g/kg/d) HSYLF groups exhibited a marked elevation in serum anti-müllerian hormone levels (low-dose group: 2657.63 ± 354.82 PG/ml; high-dose group: 2823.73 ± 316.04 PG/ml) and mitochondrial membrane potential compared to the model blank group (P < 0.05 or P < 0.01), along with a significant decline in fluorescence intensity of 2',7'-dichlorofluorescein for the levels of ROS in oocytes (P < 0.05 or P < 0.01). Additionally, both groups showed varying degrees of improvement in the morphology, quantity, and distribution of mitochondria.</p><p><strong>Conclusion: </strong>This study provides definite evidence for the molecular mechanism by which HSYLF treats POI by decreasing mitochondrial ROS, increasing membrane potential, and improving mitochondrial function. The results from active components of HSYLF and their related key targets also confirme","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"254"},"PeriodicalIF":3.8,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895531","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":"Extracellular vesicles-derived MicroRNA-145-5p is upregulated in the uterine fluid of women with endometriosis and impedes mouse and human blastocyst development.","authors":"Xiong Li, Jing Fu, Wanjun Jiang, Wenbi Zhang, Yan Xu, Ruihuan Gu, Ronggui Qu, Yaoyu Zou, Zhichao Li, Yijuan Sun, Xiaoxi Sun","doi":"10.1186/s13048-024-01579-x","DOIUrl":"10.1186/s13048-024-01579-x","url":null,"abstract":"<p><p>Previous work indicated that the implantation and pregnancy rates of women with endometriosis are lower than those of healthy women during in-vitro fertilisation and embryonic transfer. And there are numerous microRNAs (miRNAs) in human uterine luminal fluid (ULF), some of which are associated with early preimplantation development of embryos. In our study, we sought to determine whether miRNAs in the ULF are differentially expressed between women with and without endometriosis and to uncover the association of miRNAs with the development potential of blastocysts. The implantation and clinical pregnancy rates significantly decreased in women with endometriosis than in those without endometriosis. Notably, hsa-miR-145-5p was upregulated in ULF samples from women with endometriosis (fold change > 2, false discovery rate < 0.001). Moreover, the ratios of mouse/human early embryos that developed into blastocyst-staged embryos (P = 0.0065 and P = 0.0098, respectively) were significantly affected via miR-145-5p upregulation in mouse/human early embryos. Notch signalling pathway components had abnormal expression levels in the mouse/human blastocyst-stage embryos in the miR-145-5p mimic-enriched extracellular vesicles (EVs) group. In conclusions, our study revealed that human extracellular vesicle-derived miRNAs in ULF impacted the developmental potential of blastocysts in women with endometriosis. Moreover, the upregulation of miR-145-5p-enriched EVs in mouse and human embryos negatively affected blastocyst development by suppressing the expression of components of the NOTCH signalling pathway, which may contribute to elucidate the cause of infertility in women with endometriosis.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"253"},"PeriodicalIF":3.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882164","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}
Fengzhen Chen, Yanying Xu, Xiangyu Liu, Na Dong, Lei Tian
{"title":"TIGIT<sup>+</sup> CD4<sup>+</sup> regulatory T cells enhance PD-1 expression on CD8<sup>+</sup> T cells and promote tumor growth in a murine ovarian cancer model.","authors":"Fengzhen Chen, Yanying Xu, Xiangyu Liu, Na Dong, Lei Tian","doi":"10.1186/s13048-024-01578-y","DOIUrl":"10.1186/s13048-024-01578-y","url":null,"abstract":"<p><p>Immune checkpoint-based immunotherapy has shown limited efficacy in the treatment of ovarian cancer. In recent years, the emergence of immune checkpoint co-targeting therapies, led by the combination targeting of TIGIT and FAK, has shown promise in ovarian cancer treatment. Our preliminary research indicates that TIGIT is predominantly expressed in regulatory T cells during ovarian cancer. However, the therapeutic impact of TIGIT targeting based on regulatory T cells in ovarian cancer remains to be elucidated. We utilized ID8 cells to establish a mouse model of ovarian cancer. Through flow cytometry and co-culture methods, we validated the relationship between the functionality of regulatory T cells and tumor masses, and confirmed the crucial role of TIGIT in immune suppression in ovarian cancer. Furthermore, using Foxp3-diphtheria toxin receptor (DTR) mice, we substantiated that the combined TIGIT antibody treatment, based on targeting regulatory T cells, effectively slowed down the progression of ovarian cancer. Taken together, our results have demonstrated that dual targeting of regulatory T cells and TIGIT effectively retards tumor growth, laying the groundwork for the clinical application of immune checkpoint combination therapies. Future research in ovarian cancer immunotherapy is leaning towards a strategy that combines multiple targets, and specific cell-type immunotherapies.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"252"},"PeriodicalIF":3.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872254","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}
Shu Ding, Wenyan Li, Xianglei Xiong, Manfei Si, Chuyu Yun, Yuqian Wang, Lixuan Huang, Sen Yan, Xiumei Zhen, Jie Qiao, Xinyu Qi
{"title":"Bile acids in follicular fluid: potential new therapeutic targets and predictive markers for women with diminished ovarian reserve.","authors":"Shu Ding, Wenyan Li, Xianglei Xiong, Manfei Si, Chuyu Yun, Yuqian Wang, Lixuan Huang, Sen Yan, Xiumei Zhen, Jie Qiao, Xinyu Qi","doi":"10.1186/s13048-024-01573-3","DOIUrl":"10.1186/s13048-024-01573-3","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the changes in bile acid (BA) metabolites within the follicular fluid (FF) of patients with diminished ovarian reserve (DOR) and to identify novel diagnostic markers that could facilitate early detection and intervention in DOR patients.</p><p><strong>Design: </strong>A total of 182 patients undergoing assisted reproductive technology (ART) were enrolled and categorized into the normal ovarian reserve (NOR) group (n = 91) or the DOR group (n = 91) to measure BA levels in FF. To identify the changes in granulosa cells (GCs), we collected GCs from an additional 7 groups of patients for transcriptome sequencing.</p><p><strong>Setting: </strong>Reproductive medicine center within a hospital and university research laboratory.</p><p><strong>Population: </strong>A total of 182 patients undergoing assisted reproductive technology were enrolled and categorized into the NOR group (n = 91) or the DOR group (n = 91).</p><p><strong>Methods: </strong>In this study, BA metabolites in FF of DOR and NOR patients were analyzed in detail by targeted metabolomics, and the correlation between BA levels in FF and clinical indicators was discussed. Then, we constructed a diagnostic model for DOR using the random forest algorithm based on five different BAs. Additionally, we performed a functional enrichment analysis on differentially expressed genes (DEGs) in GCs from both DOR and NOR patients.</p><p><strong>Main outcome measures: </strong>BA levels in FF and their correlation with clinical indicators; the areas under the curve (AUCs) of the random forest diagnostic model for DOR; and the DEGs and corresponding functional enrichment results of GC RNA analysis.</p><p><strong>Result (s): </strong>The levels of lithocholic acid, chenodeoxycholic acid, ursodeoxycholic acid, deoxycholic acid and cholic acid in FF of DOR group were lower than those of NOR group. And significant reductions in total, primary, secondary, and unconjugated BA levels were observed in the DOR group. The above five BAs levels were closely related to indicators of ovarian reserve. The AUC of the diagnostic model based on the above five BAs was 0.964. Based on transcriptome sequencing data from two groups of GCs, a total of 482 up-regulated and 654 down-regulated DEGs were identified. Gene ontology analysis revealed that the metabolic and biosynthetic processes of fatty acids, steroids, and cholesterol were enriched in these DEGs, whereas Kyoto Encyclopedia of Genes and Genomes analysis indicated enrichment of fatty acid and ovarian steroidogenesis.</p><p><strong>Conclusion(s): </strong>The levels of multiple BA metabolites in FF are significantly lower than those in patients with DOR and are closely related to the evaluation of ovarian reserve function.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"250"},"PeriodicalIF":3.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864450","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}
Li Qin, Chun Tian, Liying Huang, Xiao Qin, Shaohua Ling, Jingxi Wei, Bingsheng Huang, Lining Li, Xiaoqiong Luo
{"title":"Clinical significance and biological roles of lncRNA CTBP1-AS in polycystic ovary syndrome.","authors":"Li Qin, Chun Tian, Liying Huang, Xiao Qin, Shaohua Ling, Jingxi Wei, Bingsheng Huang, Lining Li, Xiaoqiong Luo","doi":"10.1186/s13048-024-01571-5","DOIUrl":"10.1186/s13048-024-01571-5","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is among the most prevalent endocrine and metabolic disorders affecting women of reproductive age. Multiple factors, including genetic predisposition, environmental influences, and lifestyle choices, are considered significant contributors to the development of PCOS. A kind of long noncoding RNA-C-Terminal binding protein 1 antisense (lncRNA CTBP1-AS) has been proven to be a new androgen receptor regulator. Previous studies showed that the lncRNA CTBP1-AS gene was highly expressed in a small sample of PCOS patients and was associated with the risk of PCOS, but its specific function and mechanism have not been clearly reported. In this study, the expression of lncRNA CTBP1-AS was detected by real-time quantitative PCR (RT-qPCR) in PCOS patients. In addition, lncRNA CTBP1-AS was overexpressed in KGN cells to explore its effect on granulocyte function. The results showed that the expression levels of lncRNA CTBP1-AS were increased in peripheral blood mononuclear cells and follicular fluid granulosa cells of PCOS patients compared with controls, which correlated with androgen levels and sinus follicle number; overexpression of lncRNA CTBP1-AS increased apoptosis and decreased cell migration ability, thus promoting the progression of PCOS. This study explores new biomarkers and therapeutic targets for the clinical individualized diagnosis and treatment of PCOS.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"248"},"PeriodicalIF":3.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864454","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":"Metformin protects prepubertal mice ovarian reserve against cyclophosphamide via regulation of the PI3K/Akt/mTOR signaling pathway and Yap-1.","authors":"Negin Zatalian, Azam Dalman, Parvaneh Afsharian, Maryam Hezavehei, Hamid Gourabi","doi":"10.1186/s13048-024-01572-4","DOIUrl":"10.1186/s13048-024-01572-4","url":null,"abstract":"<p><strong>Background: </strong>Cyclophosphamide is a widely utilized chemotherapeutic agent for pediatric cancers, known to elicit adverse effects, including perturbation of the PI3K/Akt/mTOR and Hippo signaling pathways, thereby diminishing ovarian reserve and fertility potential in females. Consequently, this investigation delves into the mitigative effects of metformin on cyclophosphamide-induced ovarian impairment in prepubertal mice.</p><p><strong>Methods: </strong>Twenty-four 14-day-old NMRI female mice were distributed into four groups: Control (Cont), Cyclophosphamide (Cyc), Metformin (Met), and Metformin plus Cyclophosphamide (Met-Cyc). The Met-Cyc group was given daily doses of 150 mg/kg metformin for 11 consecutive days and in parallel 3 intermittent doses of 65 mg/kg cyclophosphamide once every three days. The Met and Cyc groups were given identical doses of Met or Cyc alone. The control group received normal saline treatment. On the 12<sup>th</sup> day, mice were sacrificed for analysis. Stereological methods were employed to measure the overall volume of the ovaries, including the medulla, cortex, and follicles, along with measuring anti-Müllerian hormone (AMH) levels using an ELISA kit. Furthermore, qRT-PCR was utilized to quantify the expression levels of genes, including P53, Bax, Bcl-2, Rad-51, Pten, Mtor, and Yap-1.</p><p><strong>Results: </strong>The findings demonstrate that metformin ameliorates cyclophosphamide-induced ovarian toxicity by increasing AMH levels and attenuating the excessive activation of primordial follicles, the ratio of growing to quiescent follicles, and follicular atresia. This protective effect is mediated by the downregulation of apoptosis-related genes, upregulation of the gene involved in a reparative pathway, and modulation of the PI3K/Akt/mTOR pathway evidenced by increased expression of Pten, Mtor and Hippo pathway by Yap-1 expression.</p><p><strong>Conclusions: </strong>Our results advocate for the potential of metformin as a viable therapeutic option for preserving ovarian function in cyclophosphamide-treated adolescent girls, given its favorable side effect profile and ability to improve cyclophosphamide-induced ovarian damage.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"251"},"PeriodicalIF":3.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864510","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":"Adipocyte-derived CXCL10 in obesity promotes the migration and invasion of ovarian cancer cells.","authors":"Zhe Wang, Qingjian Ou, Ying Liu, Yuanyuan Liu, Qingwei Zhu, Jingqiu Feng, Fengze Han, Lu Gao","doi":"10.1186/s13048-024-01568-0","DOIUrl":"10.1186/s13048-024-01568-0","url":null,"abstract":"<p><strong>Background: </strong>As a widespread epidemic, obesity poses a significant risk to health and leads to physiological abnormalities, including diabetes mellitus and inflammation. Obesity-induced inflammation can accelerate the development of various cancers; however, the role of obesity in the migration of ovarian carcinoma is still unclear.</p><p><strong>Results: </strong>Twenty-four commonly upregulated genes were identified from single-cell RNA sequencing datasets of both ovarian carcinoma and adipose tissue of obese humans, with the chemokine CXCL10 showing a significant increase in adipose tissues associated with obesity. And CXCL10 treated primed macrophages exhibit both direct and indirect effects on the proliferation, apoptosis, migration, and invasion of ovarian adenocarcinoma cells. The treatment of CXCL10 on the SKOV3 cells enhances FAK expression and phosphorylation, thereby accelerating the migration and invasion of ovarian cancer cells. Conditioned medium-derived from CXCL10-treated THP-1 cells significantly promoted ovarian cancer cell migration and invasion, which may be attributed to the increased expression of C1QA, C1QC, CCL24, and IL4R in macrophages.</p><p><strong>Conclusions: </strong>Obesity exacerbates the production of CXCL10 from adipose tissues in obese women. CXCL10 is a key hub factor between developments of ovarian cancer and adipose tissues in obese. Targeting adipose-derived CXCL10 or its downstream macrophages may be a potential strategy to alleviate ovarian cancer accompanied by obesity.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"245"},"PeriodicalIF":3.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864447","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}
Zhaoying Chen, Chenxi Zhang, Chunfeng Meng, Yadan Hu, Yazhuo Niu, Bingrui Gao, Jinshuo Wang, Lu Liu, Kan Chen, Zhongyan Shan, Weiping Teng, Jing Li
{"title":"Unveiling the link: anti-protein disulfide isomerase A3 autoantibody expression and polycystic ovary syndrome risk in euthyroid autoimmune thyroiditis women.","authors":"Zhaoying Chen, Chenxi Zhang, Chunfeng Meng, Yadan Hu, Yazhuo Niu, Bingrui Gao, Jinshuo Wang, Lu Liu, Kan Chen, Zhongyan Shan, Weiping Teng, Jing Li","doi":"10.1186/s13048-024-01569-z","DOIUrl":"10.1186/s13048-024-01569-z","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a common complication of autoimmune thyroiditis (AIT) in women, but the underlying mechanism remains unclear. Protein disulfide isomerase A3 (PDIA3) is a ubiquitous protein. We have reported that PDIA3 autoantibody (PDIA3Ab) production results from autoimmune responses against thyrocytes, resulting in its high expression in euthyroid AIT patients. This study aimed to explore potential correlations between PDIA3Ab expression and concurrent PCOS in euthyroid AIT women.</p><p><strong>Methods: </strong>This is a single-center cross-sectional study. All participants, who visited the First Hospital of China Medical University from April 2023 to May 2024, were assigned to four groups according to AIT and PCOS diagnostic criteria. The PDIA3Ab levels of total IgG and IgG subclasses were detected using ELISA.</p><p><strong>Results: </strong>From highest to lowest, PDIA3Ab total serum IgG levels were categorized as follows: AIT-PCOS group > AIT-non-PCOS group > non-AIT-PCOS group > non-AIT-non-PCOS group Significant differences were observed between each pair of groups, except for the non-AIT-PCOS and non-AIT-non-PCOS groups. Further analysis of the subclasses of PDIA3Ab revealed that serum IgG1 levels in the AIT-PCOS and AIT-non-PCOS groups were significantly higher than those in the non-AIT-PCOS and non-AIT-non-PCOS groups. In addition, the AIT-PCOS group had significantly higher serum IgG3 levels than the other three groups. Binary logistic regression analysis revealed that the PDIA3Ab total IgG level was an independent risk factor for concurrent PCOS in euthyroid AIT women (Q4 vs. Q1: OR, 95%CI = 5.082, 1.348-19.16). Furthermore, a trend test demonstrated a titer-dependent increase in PCOS prevalence among AIT women as the PDIA3Ab total IgG level increased.</p><p><strong>Conclusions: </strong>The expression of serum PDIA3Ab may indicate an increased risk of PCOS in euthyroid AIT women and could potentially serve as new targets for markers or immune intervention.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"247"},"PeriodicalIF":3.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864553","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}