BMAL1 improves assisted reproductive technology outcomes in patients with polycystic ovary syndrome by targeting BMP6 and regulating ovarian granulosa cell apoptosis.

IF 3.2 3区医学 Q2 GENETICS & HEREDITY

Journal of Assisted Reproduction and Genetics Pub Date : 2025-01-24 DOI:10.1007/s10815-024-03377-2

Qihui Liang, Chaofeng Wei, Lu Guan, Wen Chen, Shengyong Ding, Haicui Wu

{"title":"BMAL1 improves assisted reproductive technology outcomes in patients with polycystic ovary syndrome by targeting BMP6 and regulating ovarian granulosa cell apoptosis.","authors":"Qihui Liang, Chaofeng Wei, Lu Guan, Wen Chen, Shengyong Ding, Haicui Wu","doi":"10.1007/s10815-024-03377-2","DOIUrl":null,"url":null,"abstract":"Purpose: To investigate BMAL1 and BMP6 expressive differences in ovarian granulosa cells (OGCs) of patients with polycystic ovary syndrome (PCOS), explore regulatory relationship, assess their impacts on OGC proliferation and apoptosis, and analyze their correlations with ART outcomes of patients.Methods: A clinical study selected 40 PCOS patients who underwent IVF/ICSI in our hospital from January to October 2022 and 39 controls with male or tubal factor infertility. RT-qPCR and Western blot assessed BMAL1 and BMP6 mRNA/protein levels. The number of oocytes retrieved, 2PN fertilized oocytes, available embryos, and high-quality embryos were compared between groups and analyzed their correlations with BMAL1 and BMP6 expression levels. Cellular experiments were performed by overexpressing or knocking down BMAL1 in KGN cells by plasmid transfection. The dual-luciferase reporter assay was used to identify BMAL1/BMP6 regulatory relationship. CCK-8 and flow cytometry assessed cellular proliferation and apoptosis.Results: BMAL1 mRNA/protein expression (P < 0.001) in the PCOS group was significantly lower than that in controls, as was the number of high-quality embryos (P = 0.001). Contrastingly, BMP6 (P < 0.001) was significantly higher in the PCOS group. BMAL1 expression levels were negatively correlated with BMP6 (r = - 0.684, P = 0.002) and positively correlated with the number of 2PN fertilized oocytes, available embryos, and high-quality embryos (r = 0.659, P = 0.003; r = 0.623, P = 0.006; and r = 0.738, P < 0.001). Cellular experiments showed that overexpression of BMAL1 significantly decreased relative luciferase activity (P < 0.01). Overexpression of BMAL1 significantly decreased KGN cell apoptosis (P < 0.01) and enhanced proliferation (P < 0.01).Conclusion: BMAL1 regulates OGCs proliferation and apoptosis by targeting BMP6, thereby influencing ART outcomes in patients with PCOS. This study might provide molecular factors that indicate ART outcomes and therapeutic targets for PCOS.Trial registration: Registration number: ChiCTR2100052331; registration date: 2021-10-24.","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Assisted Reproduction and Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10815-024-03377-2","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

Abstract

Purpose: To investigate BMAL1 and BMP6 expressive differences in ovarian granulosa cells (OGCs) of patients with polycystic ovary syndrome (PCOS), explore regulatory relationship, assess their impacts on OGC proliferation and apoptosis, and analyze their correlations with ART outcomes of patients.

Methods: A clinical study selected 40 PCOS patients who underwent IVF/ICSI in our hospital from January to October 2022 and 39 controls with male or tubal factor infertility. RT-qPCR and Western blot assessed BMAL1 and BMP6 mRNA/protein levels. The number of oocytes retrieved, 2PN fertilized oocytes, available embryos, and high-quality embryos were compared between groups and analyzed their correlations with BMAL1 and BMP6 expression levels. Cellular experiments were performed by overexpressing or knocking down BMAL1 in KGN cells by plasmid transfection. The dual-luciferase reporter assay was used to identify BMAL1/BMP6 regulatory relationship. CCK-8 and flow cytometry assessed cellular proliferation and apoptosis.

Results: BMAL1 mRNA/protein expression (P < 0.001) in the PCOS group was significantly lower than that in controls, as was the number of high-quality embryos (P = 0.001). Contrastingly, BMP6 (P < 0.001) was significantly higher in the PCOS group. BMAL1 expression levels were negatively correlated with BMP6 (r = - 0.684, P = 0.002) and positively correlated with the number of 2PN fertilized oocytes, available embryos, and high-quality embryos (r = 0.659, P = 0.003; r = 0.623, P = 0.006; and r = 0.738, P < 0.001). Cellular experiments showed that overexpression of BMAL1 significantly decreased relative luciferase activity (P < 0.01). Overexpression of BMAL1 significantly decreased KGN cell apoptosis (P < 0.01) and enhanced proliferation (P < 0.01).

Conclusion: BMAL1 regulates OGCs proliferation and apoptosis by targeting BMP6, thereby influencing ART outcomes in patients with PCOS. This study might provide molecular factors that indicate ART outcomes and therapeutic targets for PCOS.

Trial registration: Registration number: ChiCTR2100052331; registration date: 2021-10-24.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Assisted Reproduction and Genetics 医学-妇产科学

CiteScore

5.70

自引率

9.70%

发文量

286

审稿时长

1 months

期刊介绍： The Journal of Assisted Reproduction and Genetics publishes cellular, molecular, genetic, and epigenetic discoveries advancing our understanding of the biology and underlying mechanisms from gametogenesis to offspring health. Special emphasis is placed on the practice and evolution of assisted reproduction technologies (ARTs) with reference to the diagnosis and management of diseases affecting fertility. Our goal is to educate our readership in the translation of basic and clinical discoveries made from human or relevant animal models to the safe and efficacious practice of human ARTs. The scientific rigor and ethical standards embraced by the JARG editorial team ensures a broad international base of expertise guiding the marriage of contemporary clinical research paradigms with basic science discovery. JARG publishes original papers, minireviews, case reports, and opinion pieces often combined into special topic issues that will educate clinicians and scientists with interests in the mechanisms of human development that bear on the treatment of infertility and emerging innovations in human ARTs. The guiding principles of male and female reproductive health impacting pre- and post-conceptional viability and developmental potential are emphasized within the purview of human reproductive health in current and future generations of our species. The journal is published in cooperation with the American Society for Reproductive Medicine, an organization of more than 8,000 physicians, researchers, nurses, technicians and other professionals dedicated to advancing knowledge and expertise in reproductive biology.