{"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}
Lijun Lin, Ge Chen, Xiaoyong Qiao, Yan Chen, Hongxia Deng, Liangzhi Xu
{"title":"Comparative efficacy and safety of metformin, anti-obesity agents, and myoinositol in improving IVF/ICSI outcomes and reducing ovarian hyperstimulation syndrome in women with polycystic ovary syndrome: a systematic review and network meta-analysis.","authors":"Lijun Lin, Ge Chen, Xiaoyong Qiao, Yan Chen, Hongxia Deng, Liangzhi Xu","doi":"10.1186/s13048-024-01576-0","DOIUrl":"10.1186/s13048-024-01576-0","url":null,"abstract":"<p><strong>Purpose: </strong>To compare the efficacy and safety of metformin, anti-obesity agents, and inositol with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).</p><p><strong>Methods: </strong>A comprehensive search was conducted in PubMed, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov for studies published in English up to October 26, 2024. Randomized controlled trials (RCTs) evaluating metformin, anti-obesity agents, and inositol were included. A network meta-analysis was performed using frequency statistical methods. Subgroup analyses were conducted based on controlled ovarian stimulation (COS) protocols and body mass index(BMI). The research protocol was registered with PROSPERO (registration code CRD42024502823).</p><p><strong>Results: </strong>20 RCTs were included with 1,827 patients assessed six different agents. Nineteen trials were rated low risk, with one rated moderate risk. Pairwise meta-analysis showed that metformin did not improve pregnancy outcomes but was associated with a reduced ovarian hyperstimulation syndrome (OHSS) risk (OR = 0.52, 95% CI 0.33-0.83), particularly in agonist protocols, along with lower E2 levels on the trigger day (SMD = -0.56, 95% CI -0.90 to -0.21) and increased side effects (OR = 6.85, 95% CI 4.32-10.86). Network meta-analysis confirmed no significant differences in pregnancy outcomes for these agents compared to controls, though both myoinositol and metformin reduced OHSS risk. Myoinositol was linked to a shorter gonadotropin duration (SMD = -1.21, 95% CI -2.03 to -0.38) and fewer side effects (OR = 0.23, 95% CI 0.06-0.83) compared to controls. Metformin led to lower E2 levels, a higher number of mature oocytes, and increased side effects (SMD = -376.52, 95% CI -610.83 to -142.22; SMD = 2.23, 95% CI 0.36-4.10; OR = 6.85, 95% CI 4.32-10.86) than controls. No studies reported an increased risk of fetal abnormalities.</p><p><strong>Conclusion: </strong>Metformin and myoinositol may reduce OHSS risk in PCOS patients but did not significantly improve pregnancy outcomes. Metformin may lower OHSS risk in agonist protocol, reduce E2 levels on trigger day and increase mature oocytes but cause more side effects, while myoinositol may shorten gonadotropin duration with fewer side effects. Further robust RCTs are needed to confirm these findings.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"249"},"PeriodicalIF":3.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864504","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}
Xue Sui, Bingqing Gao, Liu Zhang, Yanmin Wang, Junnan Ma, Xingchen Wu, Chenyu Zhou, Min Liu, Lin Zhang
{"title":"Scutellaria barbata D.Don and Hedyotis diffusa Willd herb pair combined with cisplatin synergistically inhibits ovarian cancer progression through modulating oxidative stress via NRF2-FTH1 autophagic degradation pathway.","authors":"Xue Sui, Bingqing Gao, Liu Zhang, Yanmin Wang, Junnan Ma, Xingchen Wu, Chenyu Zhou, Min Liu, Lin Zhang","doi":"10.1186/s13048-024-01570-6","DOIUrl":"10.1186/s13048-024-01570-6","url":null,"abstract":"<p><strong>Background: </strong>Cisplatin (DDP) is one of the most effective anticancer drugs, commonly used to treat advanced ovarian cancer (OC). However, DDP has significant limitations of platinum-based drugs, including chemical resistance and high-dose toxic side effects. Traditional Chinese medicines (TCMs) often presented in the form of formula, in which the herb pair was the basic unit. Scutellaria barbata D.Don and Hedyotis diffusa Willd (SB-HD) are famous TCMs herb pair that have been shown to help treat multiple types of cancers. However, the synergistic effects and mechanism of combination of SB-HD and DDP to enhance DDP chemosensitivity in OC are still unknown.</p><p><strong>Results: </strong>In vitro, we found that the optimal proportion of SB-HD to inhibit the proliferation of OC cells was 2:1, SB-HD and DDP were shown to synergistically reduce the viability of OC cells, inhibit the colony formation, promote cell cycle arrest and apoptosis, as well as inhibit cell migration and invasion. In vivo, combination treatment significantly inhibited the growth of subcutaneous tumors in BALB/c nude mice and reduced the toxic side effects of DDP. Mechanistically, SB-HD and DDP combination treatment significantly promoted oxidative stress response, decreased MMP, inhibited ATP production, decreased ROS levels and increased SOD activity, increased the expression of NRF2, HO-1, ATG5 and LC3, decreased the expression of p62 and FTH1 both in OC cells and tumor tissue of mice. Inhibitor 3-MA (Methyladenine, autophagy inhibitor) and Fer-1 (Ferrostatin-1, iron ion inhibitor) can effectively reverse the expression changes of the key target proteins, but not ZnPP (Zinc protoporphyrin, HO-1 inhibitor). Through bioinformatics analysis, it was found that the abnormal expression level of NRF2 and FTH1 mRNA has a high prognostic value, at the same time, the other four key proteins respectively or interacting with NRF2 and FTH1, also play important roles in the occurrence and development of OC.</p><p><strong>Conclusion: </strong>Our findings uncover a synergistic effect of SB-HD and DDP against OC through modulating oxidative stress via NRF2-FTH1 autophagic degradation pathway, which may provide an important theoretical foundation for the use of SB-HD and a new strategy for enhancing DDP chemosensitivity as well as reducing toxic side effects.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"246"},"PeriodicalIF":3.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864515","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 melanocortin receptor genes are linked to and associated with the risk of polycystic ovary syndrome in Italian families.","authors":"Rongling Wu, Claudia Gragnoli","doi":"10.1186/s13048-024-01567-1","DOIUrl":"10.1186/s13048-024-01567-1","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is the most common endocrine disorder occurring in women of reproductive age. The disease is caused by a complex interplay of genetic and environmental factors including genes encoding components of the hypothalamic-pituitary-adrenal (HPA) axis. We have recently reported the association of melanocortin receptor genes (MC1R, MC2R, MC3R, MC4R, and MC5R) with the risk of type 2 diabetes (T2D) and/or major depressive disorder (MDD). The latter 2 disorders are comorbid with PCOS. In this study, we used microarray to test 12 single nucleotide polymorphisms (SNPs) in the MC1R gene, 10 SNPs in the MC2R gene, 5 SNPs in the MC3R gene, 6 SNPs in the MC4R gene, and 4 SNPs in the MC5R gene in 212 original Italian families with PCOS. We identified 1 SNP in MC1R, 1 SNP in MC2R, 2 SNPs in MC3R, and 2 SNPs in MC5R significantly linked and/or associated to/with the risk of PCOS in Italian families. This is the first study to report the novel implication of melanocortin receptor genes (MC1R, MC2R, and MC5R) in PCOS. MC3R and MC4R were previously reported in PCOS. However, functional studies are needed to validate these results.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"242"},"PeriodicalIF":3.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780409","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":"Exploring the innovative application of cerium oxide nanoparticles for addressing oxidative stress in ovarian tissue regeneration.","authors":"Maya Lakshmanan, Monika Saini, Manasa Nune","doi":"10.1186/s13048-024-01566-2","DOIUrl":"10.1186/s13048-024-01566-2","url":null,"abstract":"<p><p>The female reproductive system dysfunction considerably affects the overall health of women and children on a global scale. Over the decade, the incidence of reproductive disorders has become a significant source of suffering for women. Infertility in women may be caused by a range of acquired and congenital abnormalities. Ovaries play a central role in the female reproductive function. Any defect in the normal functioning of these endocrine organs causes health issues and reproductive challenges extending beyond infertility, as the hormones interact with other tissues and biological processes in the body. The complex pathophysiology of ovarian disorders makes it a multifactorial disease. The key etiological factors associated with the diseases include genetic factors, hormonal imbalance, environmental and lifestyle factors, inflammatory conditions, oxidative stress, autoimmune diseases, metabolic factors, and age. Oxidative stress is a major contributor to disease development and progression affecting the oocyte quality, fertilization, embryo development, and implantation. The choice of treatment for ovarian disorders varies among individuals and has associated complications. Reproductive tissue engineering holds great promise for overcoming the challenges associated with the current therapeutic approach to tissue regeneration. Furthermore, incorporating nanotechnology into tissue engineering could offer an efficient treatment strategy. This review provides an overview of incorporating antioxidant nanomaterials for engineering ovarian tissue to address the disease recurrence and associated pathophysiology. Cerium oxide nanoparticles (CeO<sub>2</sub> NPs) are prioritized for evaluation primarily due to their antioxidant properties. In conclusion, the review explores the potential applications of CeO<sub>2</sub> NPs for effective and clinically significant ovarian tissue regeneration.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"241"},"PeriodicalIF":3.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780398","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}
Kaylin M Carey, Corey D Young, Alexis J Clark, Eric B Dammer, Rajesh Singh, James W Lillard
{"title":"Subtype-specific analysis of gene co-expression networks and immune cell profiling reveals high grade serous ovarian cancer subtype linkage to variable immune microenvironment.","authors":"Kaylin M Carey, Corey D Young, Alexis J Clark, Eric B Dammer, Rajesh Singh, James W Lillard","doi":"10.1186/s13048-024-01556-4","DOIUrl":"10.1186/s13048-024-01556-4","url":null,"abstract":"<p><p>High-grade serous ovarian cancer (HGSOC) is marked by significant molecular diversity, presenting a major clinical challenge due to its aggressive nature and poor prognosis. This study aims to deepen the understanding of HGSOC by characterizing mRNA subtypes and examining their immune microenvironment (TIME) and its role in disease progression. Using transcriptomic data and an advanced computational pipeline, we investigated four mRNA subtypes: immunoreactive, differentiated, proliferative, and mesenchymal, each associated with distinct gene expression profiles and clinical behaviors. We performed differential expression analysis among mRNA subtypes using DESeq2 and conducted Weighted Gene Co-Expression Network Analysis (WGCNA) to identify co-expressed gene modules related to clinical traits, e.g., age, survival, and subtype classification. Gene Ontology (GO) analysis highlighted key pathways involved in tumor progression and immune evasion. Additionally, we utilized TIMER 2.0 to assess immune cell infiltration across different HGSOC subtypes, providing insights into the interplay between tumor immune microenvironment (TIME). Our findings show that the immunoreactive subtype, particularly the M3 module-associated network, was marked by high immune cell infiltration, including M1 (p < 0.0001) and M2 macrophages (p < 0.01), and Th1 cells (p < 0.01) along with LAIR-1 expression (p = 1.63e-101). The M18 module exhibited strong B cell signatures (p = 6.24e-28), along with significant FCRL5 (adj. p = 3.09e-30) and IRF4 (adj. p = 3.09e-30) coexpression. In contrast, the M5 module was significantly associated with the mesenchymal subtype, along with fibroblasts (p < 0.0001). The proliferative subtype was characterized by M15 module-driven cellular growth and proliferation gene expression signatures, along with significant ovarian stromal cell involvement (p < 0.0001). Our study reveals the complex interplay between mRNA subtypes and suggests genes contributing to molecular subtypes, underscoring the important clinical implications of mRNA subtyping in HGSOC.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"240"},"PeriodicalIF":3.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11613732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769872","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}
Amany I Ahmed, Mohamed F Dowidar, Asmaa F Negm, Hussein Abdellatif, Asma Alanazi, Mohammed Alassiri, Walaa Samy, Dina Mohamed Mekawy, Eman M A Abdelghany, Nesma I El-Naseery, Mohamed A Ibrahem, Emad Ali Albadawi, Wed Salah, Mamdouh Eldesoqui, Emil Tîrziu, Iulia Maria Bucur, Ahmed Hamed Arisha, Tarek Khamis
{"title":"Correction: Bone marrow mesenchymal stem cells expressing Neat-1, Hotair-1, miR-21, miR-644, and miR-144 subsided cyclophosphamide-induced ovarian insufficiency by remodeling the IGF-1-kisspeptin system, ovarian apoptosis, and angiogenesis.","authors":"Amany I Ahmed, Mohamed F Dowidar, Asmaa F Negm, Hussein Abdellatif, Asma Alanazi, Mohammed Alassiri, Walaa Samy, Dina Mohamed Mekawy, Eman M A Abdelghany, Nesma I El-Naseery, Mohamed A Ibrahem, Emad Ali Albadawi, Wed Salah, Mamdouh Eldesoqui, Emil Tîrziu, Iulia Maria Bucur, Ahmed Hamed Arisha, Tarek Khamis","doi":"10.1186/s13048-024-01564-4","DOIUrl":"10.1186/s13048-024-01564-4","url":null,"abstract":"","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"239"},"PeriodicalIF":3.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755254","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}