{"title":"Mesenchymal stem cell-derived extracellular vesicles therapy for primary ovarian insufficiency: a systematic review and meta-analysis of pre-clinical studies.","authors":"Shahryar Rajai Firouzabadi, Ida Mohammadi, Kiana Ghafourian, Seyed Ali Mofidi, Shahrzad Rajaei Firouzabadi, Seyed Mahmoud Hashemi, Fahimeh Ramezani Tehrani, Kyana Jafarabady","doi":"10.1186/s13048-024-01513-1","DOIUrl":"10.1186/s13048-024-01513-1","url":null,"abstract":"<p><strong>Background: </strong>Primary ovarian insufficiency (POI) manifests with hormonal imbalances, menstrual irregularities, follicle loss, and infertility. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are emerging as a promising treatment for POI. This systematic review aims to assess the effects of MSC-EVs on follicle number, hormonal profile, and fertility in POI animal models.</p><p><strong>Methods: </strong>A systematic search of PubMed, Scopus, and Web of Science databases up to December 14th, 2023 was conducted. Two reviewers independently conducted screening, risk of bias assessment, and data extraction. Meta-analysis was performed to analyze treatment versus control outcomes using a random effects model. Publication bias was assessed using Egger's regression test and sensitivity analysis was assessed using the leave-one-out method. Subgroup analyses and meta-regressions were conducted based on EV source, induction model, type of animal, study quality, administration route, administration frequency and route, and dose.</p><p><strong>Results: </strong>a total of 29 studies were included. MSC-EVs treatment significantly increased total follicle count (SMD, (95CI), p-value; 3.56, (0.91, 6.21), < 0.001), including primordial (SMD, (95CI), p-value; 2.86, (1.60, 4.12), < 0.001), primary (SMD, (95CI), p-value; 3.17, (2.28, 4.06), < 0.001), mature (SMD, (95CI), p-value; 2.26, (1.02, 3.50), < 0.001), and antral follicles (SMD, (95CI), p-value; 2.44, (1.21, 3.67), < 0.001). Administration frequency and route did not affect this outcome, but EV source affected primordial, primary, secondary and antral follicle count. Additionally, MSC-EVs treatment elevated anti-müllerian hormone (SMD, (95CI); 3.36, (2.14, 4.58)) and estradiol (SMD, (95CI); 3.19, (2.20, 4.17)) levels while reducing follicle stimulating hormone levels (SMD, (95CI); -2.68, (-4.42, -0.94)). Unlike EV source, which had a significant impact on all three hormones, administration frequency, route, and EV dose did not affect this outcome. Moreover, treatment increased offspring number (SMD, (95CI); 3.70, (2.17, 5.23)) and pregnancy odds (OR, (95CI); 10.25, (4.29, 24.46)) compared to controls. Publication bias and a high level of heterogeneity was evident in all analyses, except for the analysis of the pregnancy odds. However, sensitivity analysis indicated that all of the analyses were stable.</p><p><strong>Conclusion: </strong>MSC-EVs therapy shows promise for POI treatment, potentially facilitating clinical translation. However, Further research is warranted to optimize methodology and assess side effects.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"200"},"PeriodicalIF":3.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468065","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":"Nanotechnology for boosting ovarian cancer immunotherapy.","authors":"Prabhjot Kaur, Santosh Kumar Singh, Manoj K Mishra, Shailesh Singh, Rajesh Singh","doi":"10.1186/s13048-024-01507-z","DOIUrl":"https://doi.org/10.1186/s13048-024-01507-z","url":null,"abstract":"<p><p>Ovarian cancer, often referred to as the \"silent killer,\" is notoriously difficult to detect in its early stages, leading to a poor prognosis for many patients. Diagnosis is often delayed until the cancer has advanced, primarily due to its ambiguous and frequently occurring clinical symptoms. Ovarian cancer leads to more deaths than any other cancer of the female reproductive system. The main reasons for the high mortality rates include delayed diagnosis and resistance to treatment. As a result, there is an urgent need for improved diagnostic and treatment options for ovarian cancer. The standard treatments typically involve debulking surgery along with platinum-based chemotherapies. Among patients with advanced-stage cancer who initially respond to current therapies, 50-75% experience a recurrence. Recently, immunotherapy-based approaches to enhance the body's immune response to combat tumor growth have shown promise. Immune checkpoint inhibitors have shown promising results in treating other types of tumors. However, in ovarian cancer, only a few of these inhibitors have been effective because the tumor's environment suppresses the immune system and creates barriers for treatment. This hampers the effectiveness of existing immunotherapies. Nonetheless, advanced immunotherapy techniques and delivery systems based on nanotechnology hold promise for overcoming these challenges.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"202"},"PeriodicalIF":3.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11475952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468067","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}
Kusum Kumar, Katherine Bosch, Vasa Vemuri, Nicholas Kratholm, Madhavi Rane, Sham S Kakar
{"title":"Withaferin A ameliorates ovarian cancer-induced renal damage through the regulation of expression of inflammatory cytokines.","authors":"Kusum Kumar, Katherine Bosch, Vasa Vemuri, Nicholas Kratholm, Madhavi Rane, Sham S Kakar","doi":"10.1186/s13048-024-01519-9","DOIUrl":"10.1186/s13048-024-01519-9","url":null,"abstract":"<p><strong>Background: </strong>Cachexia a multifactorial syndrome is a common sequala in patients with cancer. It varies from 42 to 80% depending upon the oncological stage and is directly responsible for 30% of deaths in these patients. Previous research from our laboratory demonstrated that peritoneal ovarian cancer generated in NSG mice resulted in skeletal and cardiac muscle atrophy - leading to loss of skeletal muscle mass and strength, and cardiac dysfunction (cachexia). Treatment of mice bearing i.p. tumors with withaferin A (WFA) showed reversal of skeletal muscle and cardiac cachexia. The present study is focused on determining effects of peritoneal ovarian tumors on kidney damage and effects of WFA treatment on ameliorating kidney damage.</p><p><strong>Methods: </strong>We generated intraperitoneal ovarian cancer by injecting female NSG mice with ovarian cancer cell line (A2780). After one week of injecting cancer cells, mice were treated with WFA (4 mg/kg) every third day, for three weeks. After 4 weeks of injection of cancer cells, the mice were sacrificed and various tissues including kidney and blood were collected, snap-frozen in liquid nitrogen, and stored at -80<sup>0</sup>C. The presence of kidney biomarker creatinine, was measured in the plasma by an ELISA. The mRNA was isolated from mouse kidneys and was used to examine the expression levels of signaling proteins, inflammatory cytokines, and genes responsible for inducing cachexia (IL-1β, IL-6, TNF-α, TGF-β, GDF-15, and MYD88).</p><p><strong>Results: </strong>Our results showed a significant increase in levels of expression of inflammatory cytokine IL-1 β (p < 0.01), IL-6 (p < 0.001), TNF-α (p < 0.001), and other related genes including TRAF6 (p < 0.01), MYD88 (p < 0.01), and GDF-15 (p = 0.005) in tumor-bearing mice compared to controls. Treatment of mice bearing tumors with WFA attenuated the increase in expression of each gene. In addition, our results showed a significant increase in creatinine levels in circulation in tumor-bearing mice compared to control mice. Treatment of tumor-bearing mice with WFA resulted in a significant decrease in plasma creatinine levels compared to tumor-bearing mice.</p><p><strong>Conclusions: </strong>Our results conclude that ovarian tumors in NSG mice caused kidney damage and renal dysfunction, which was effectively ameliorated by WFA treatment, suggesting a protective effect of WFA on kidney injury induced by ovarian cancer.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"199"},"PeriodicalIF":3.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406478","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":"Investigating PPT2's role in ovarian cancer prognosis and immunotherapy outcomes.","authors":"Hui Xu, Yan Zhang, Zhen Xie, Xiao-Feng Xie, Wen-Lan Qiao, Miao Wang, Bei-Bei Zhao, Tian Hua","doi":"10.1186/s13048-024-01527-9","DOIUrl":"10.1186/s13048-024-01527-9","url":null,"abstract":"<p><p>Ovarian cancer (OC) remains the primary cause of mortality among gynecological malignancies, and the identification of reliable molecular biomarkers to prognosticate OC outcomes is yet to be achieved. The gene palmitoyl protein thioesterase 2 (PPT2), which has been sparsely studied in OC, was closely associated with metabolism. This study aimed to determine the association between PPT2 expression, prognosis, immune infiltration, and potential molecular mechanisms in OC. We obtained the RNA-seq and clinical data from The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx) and Gene Expression Omnibus (GEO) databases, then Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, nomogram, and calibration were conducted to assess and verify the role of PPT2. Gene set enrichment analysis (GSEA) was used to figure out the closely correlated pathways with PPT2. Overexpression experiment was performed to explore the function of PPT2. Our findings showed that PPT2 mRNA expression was apparent down-regulation in OC tissue compared to normal ovarian tissues in TCGA, GTEx datasets, and GEO datasets. This differential expression was also confirmed in our in-house datasets at both the mRNA and protein levels. Decreased PPT2 expression correlated with lower survival rates in TCGA, several GEO datasets, and our in-house datasets. Multivariate analysis revealed that PPT2 was an independent factor in predicting better outcomes for OC patients in TCGA and GEO. A negative correlation was revealed between immune infiltration and PPT2 expression through Single-sample GSEA (ssGSEA). Additionally, PPT2 was negatively correlated with an up-regulated immune score, stromal score, and estimate score, suggesting that patients with low PPT2 expression might benefit more from immunotherapy. Numerous chemical agents showed lower IC50 in patients with high PPT2 expression. In single-cell RNA sequencing (scRNA-seq) analysis of several OC datasets, we found PPT2 was mainly expressed in endothelial cells. Furthermore, we found that PPT2 inhibited OC cell proliferation in vitro. Our results demonstrated that PPT2 was considered a favorable prognostic biomarker for OC and may be vital in predicting response to immunotherapy and chemotherapy. Further research was needed to fully understand the relationship between PPT2 and immunotherapy efficacy in OC patients.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"198"},"PeriodicalIF":3.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406477","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":"Comprehensive in silico analysis of prognostic and immune infiltrates for FGFs in human ovarian cancer.","authors":"Yu Wang, Haiyue Zhang, Yuanyuan Zhan, Zhuoran Li, Sujing Li, Shubin Guo","doi":"10.1186/s13048-024-01496-z","DOIUrl":"10.1186/s13048-024-01496-z","url":null,"abstract":"<p><strong>Background: </strong>Fibroblast growth factors (FGFs) are cell signaling proteins that perform multiple biological processes in many biological processes (cell development, repair, and metabolism). The dynamics of tumor cells, such as angiogenesis, transformation, and proliferation, have a significant impact on neoplasia and are modulated by FGFs. FGFs' expression and prognostic significance in ovarian cancer (OC), however, remain unclear.</p><p><strong>Methods: </strong>Through a series of in silico analysis, we investigated the transcriptional, survival data, genetic variation, gene-gene interaction network, ferroptosis-related genes, and DNA methylation of FGFs in OC patients.</p><p><strong>Results: </strong>We discovered that while FGF18 expression levels were higher in OC tissues than in normal OC tissues, FGF2/7/10/17/22 expression levels were lower in the former, and that FGF1/19 expression was related to the tumor stage in OC patients. According to the survival analysis, the clinical prognosis of individuals with OC was associated with the aberrant expression of FGFs. The function of FGFs and their neighboring genes was mainly connected to the cellular response to FGF stimulus. There was a negative correlation between FGF expression and various immune cell infiltration.</p><p><strong>Conclusions: </strong>This study clarifies the relationship between FGFs and OC, which might provide new insights into the choice of prognostic biomarkers of OC patients.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"197"},"PeriodicalIF":3.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391217","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":"ADC: a deadly killer of platinum resistant ovarian cancer.","authors":"Xu Cheng, Ping Li, Rongqi Jiang, Enqing Meng, Hao Wu","doi":"10.1186/s13048-024-01523-z","DOIUrl":"10.1186/s13048-024-01523-z","url":null,"abstract":"<p><p>Platinum is a key component of ovarian cancer systemic therapy. However, most patients will eventually face a recurrence, leading to chemotherapy resistance, especially against platinum. For individuals with platinum-resistant ovarian cancer (PROC), treatment options are limited, and their survival prospects are grim. The emergence of antibody-drug conjugates (ADCs) shows promises as a future treatment for PROC. This review synthesizes current research on the effectiveness of ADCs in treating PROC. It encapsulates the advancements and clinical trials of novel ADCs that target specific antigens such as Folate Receptor alpha (FRα), MUC16, NaPi2b, Mesothelin, Dipeptidase 3(DPEP3), and human epidermal growth factor receptor 2 (HER2), as well as tissue factor, highlighting their potential anti-tumor efficacy and used in combination with other therapies. The ADCs landscape in ovarian cancer therapeutics is swiftly evolving, promising more potent and efficacious treatment avenues.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"196"},"PeriodicalIF":3.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11451100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375527","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}
Lin-Yu Chen, Yu-Ting Chou, Phui-Ly Liew, Ling-Hui Chu, Kuo-Chang Wen, Shiou-Fu Lin, Yu-Chun Weng, Hui-Chen Wang, Po-Hsuan Su, Hung-Cheng Lai
{"title":"In vitro drug testing using patient-derived ovarian cancer organoids.","authors":"Lin-Yu Chen, Yu-Ting Chou, Phui-Ly Liew, Ling-Hui Chu, Kuo-Chang Wen, Shiou-Fu Lin, Yu-Chun Weng, Hui-Chen Wang, Po-Hsuan Su, Hung-Cheng Lai","doi":"10.1186/s13048-024-01520-2","DOIUrl":"10.1186/s13048-024-01520-2","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer is the most lethal gynecological cancer. As the primary treatment, chemotherapy has a response rate of only 60-70% in advanced stages, and even lower as a second-line treatment. Despite guideline recommendations, which drugs will be most effective remains unclear. Thus, a strategy to prioritize chemotherapy options is urgently needed. Cancer organoids have recently emerged as a method for in vitro drug testing. However, limited clinical correlations have been assessed with test results from cancer organoids, particularly in gynecological cancers. We therefore aimed to generate patient-derived organoids (PDOs) of ovarian cancer, to assess their drug sensitivities and correlations with patient clinical outcomes.</p><p><strong>Methods: </strong>PDOs were generated from fresh tumors obtained during surgical resection, which was then cultured under matrix gel and appropriate growth factors. Morphological and molecular characterization of PDOs were assessed by phase contrast microscopy and paraffin-embedded histopathology. Expressions of PAX8, TP53, WT1, CK7, and CK20 were tested by immunohistochemical staining and compared with parental tumor tissues and the human protein atlas database. PDOs were subjected to in vitro drug testing to determine drug sensitivity using Titer-Glo<sup>®</sup> 3D Cell Viability Assay. PDO viability was measured, and area under the curve calculated, to compare responses to various compounds. Correlations were calculated between selected patients' clinical outcomes and in vitro drug testing results.</p><p><strong>Results: </strong>We established 31 PDOs. Among them, 28 PDOs can be expanded, including 15, 11, and 2 from ovarian, endometrial, and cervical cancers, respectively. The PDOs preserved the histopathological profiles of their originating tumors. In vitro drug testing of 10 ovarian cancer PDOs revealed individual differential responses to recommended drugs, and interpersonal heterogeneity in drug sensitivity, even with the same histology type. Among four patients who were platinum sensitive, resistant, or refractory, PDO drug responses correlated well with their clinical courses.</p><p><strong>Conclusion: </strong>In vitro drug testing using ovarian cancer organoids is feasible and correlates well with patient clinical responses. These results may facilitate development of precision chemotherapy and personalized screening for repurposed or new drugs.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"194"},"PeriodicalIF":3.8,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365556","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}
Haihong Du, Pengfei Zeng, Xuyi Liu, Jun Zhang, Zhonglu Huang
{"title":"Identifying therapeutic targets for primary ovarian insufficiency through integrated genomic analyses.","authors":"Haihong Du, Pengfei Zeng, Xuyi Liu, Jun Zhang, Zhonglu Huang","doi":"10.1186/s13048-024-01524-y","DOIUrl":"10.1186/s13048-024-01524-y","url":null,"abstract":"<p><strong>Background: </strong>Primary ovarian insufficiency (POI) is a disorder characterized by the premature decline in ovarian function, leading to significant fertility and health impacts on women under 40. The unclear etiology of POI hinders the development of effective treatments, highlighting the need for novel therapeutic targets.</p><p><strong>Methods: </strong>This study employed genome-wide association analysis (GWAS) integrated with expression quantitative trait loci (eQTL) data from the GTEx and eQTLGen databases. Mendelian randomization (MR) and colocalization analyses were conducted to investigate causal relationships between genetic variants and POI and to identify potential therapeutic targets.</p><p><strong>Results: </strong>We identified 431 genes with available index cis-eQTL signals, of which four (HM13, FANCE, RAB2A, and MLLT10) were significantly associated with POI. Colocalization analysis revealed strong evidence for FANCE and RAB2A, indicating their potential as therapeutic targets. Subsequent druggability assessments identified FANCE and RAB2A as promising candidates for POI treatment, supported by their involvement in DNA repair and autophagy regulation, respectively.</p><p><strong>Conclusions: </strong>Our study establishes a causal link between specific genes and POI, highlighting FANCE and RAB2A as potential drug targets. These findings provide a foundation for future research and therapeutic development, aiming to improve outcomes for women with POI. Validation in further trials is necessary to confirm these potential targets.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"193"},"PeriodicalIF":3.8,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365555","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}
Yuan-Li Li, En-Qi Yan, Guang-Nian Zhao, Lei Jin, Bing-Xin Ma
{"title":"Effect of body mass index on ovarian reserve and ART outcomes in infertile women: a large retrospective study.","authors":"Yuan-Li Li, En-Qi Yan, Guang-Nian Zhao, Lei Jin, Bing-Xin Ma","doi":"10.1186/s13048-024-01521-1","DOIUrl":"10.1186/s13048-024-01521-1","url":null,"abstract":"<p><strong>Background: </strong>Obesity poses a significant global health challenge, with profound implications for women's reproductive health. The relationship between ovarian reserve and body mass index (BMI) remains a subject of debate. While obesity is generally associated with poorer outcomes in assisted reproductive technology (ART), the evidence remains inconclusive. This study aimed to investigate the effect of pre-pregnancy BMI on ovarian reserve and ART outcomes in infertile patients.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study involving women who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) procedures at Tongji Hospital between 2016 and 2023. The study included 30,746 initial fresh cycles and 5,721 singleton deliveries. Patients were stratified by age and further categorized into four BMI groups: lean (< 18.5 kg/m²), normal weight (18.5-24.9 kg/m²), overweight (25.0-29.9 kg/m²), and obese (≥ 30.0 kg/m²). The primary endpoints of the study were pregnancy and perinatal outcomes. To explore the association between BMI and these outcomes, we adjusted for relevant confounding factors and utilized multivariate linear regression models, complemented by multifactorial logistic regression analyses.</p><p><strong>Results: </strong>Anti-Müllerian hormone (AMH) levels were significantly lower in the overweight and obese groups compared to the normal weight group. After adjusting for age, a negative correlation was found between AMH and BMI in the age subgroups of 20-30 and 30-35 years. Among women aged 20-35 years, those in the overweight and obese groups had significantly fewer retrieved oocytes, mature oocytes, and two-pronuclear (2PN) embryos than their normal weight counterparts. Despite these differences, pregnancy outcomes in the overweight and obese groups were comparable to those in the normal weight group across all age categories. Additionally, obesity was linked to an increased risk of gestational diabetes mellitus, hypertensive disorders of pregnancy, and macrosomia.</p><p><strong>Conclusions: </strong>An age-related decrease in AMH levels was evident with increasing BMI. Although being overweight or obese is associated with poorer embryo and perinatal outcomes, it does not seem to have a substantial impact on fertility.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"195"},"PeriodicalIF":3.8,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365554","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":"Protective effect of afamin protein against oxidative stress related injury in human ovarian granulosa cells.","authors":"Qiang Zhang, Xiaoyu Zheng, Xueying Zhang, Lianwen Zheng","doi":"10.1186/s13048-024-01511-3","DOIUrl":"10.1186/s13048-024-01511-3","url":null,"abstract":"<p><strong>Background: </strong>Ovarian granulosa cells (GCs) play crucial roles in follicular growth and development. Their normal function is influenced by various factors, including oxidative stress, which is a significant factor. Afamin protein is a vitamin E-specific binding protein that acts as a vitamin E carrier in follicular fluid. Although the mechanism of the protective effect of afamin on human ovarian GCs is still unclear, there is evidence it has an antioxidant effect in neuronal cells.</p><p><strong>Methods: </strong>In this study, we investigated the protective effects of afamin proteins on testosterone propionate (TP)-induced ovarian GCs using a human ovarian tumor granulosa cell line (KGN).</p><p><strong>Results: </strong>The results showed that afamin reduced TP-induced oxidative stress in KGN cells by decreasing the levels of oxidative damage markers, enhancing the activity of antioxidant enzymes, and exerting a protective effect on GCs. Supplementation with afamin repaired mitochondrial dysfunction by improving mitochondrial membrane potential damage and ATP levels. It counteracted TP-induced apoptosis by decreasing the activity of Caspase-3 and upregulating the expression of the anti-apoptotic gene (BCL-2) while downregulating the expression of the pro-apoptotic gene BCL-2-associated X protein (BAX). In addition, afamin regulated the expression of genes related to ovarian steroid hormone synthesis, ameliorating the endocrine dysfunction observed in TP-induced KGN cells.</p><p><strong>Conclusion: </strong>Therefore, Afamin proteins may serve as important complementary factors that protect GCs from other types of damage, such as oxidative stress, and may help improve ovarian follicle quality and female reproductive function.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"189"},"PeriodicalIF":3.8,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348611","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}