Growth hormone reduces aneuploidy and improves oocytes quality by JAK2-MAPK3/1 pathway in aged mice

Journal of Translational Medicine

Research

Xi Zeng¹  Guo-Ning Huang¹  Chong Li¹  Qiang Dong¹  Juan Xie¹  Yun-Yao Luo¹  Ling Zhu¹  Jing-Yu Li¹  Qing-Yuan Sun² 

[1]Chongqing Key Laboratory of Human Embryo Engineering, Center for Reproductive Medicine, Women and Children’s Hospital of Chongqing Medical University, 400010, Chongqing, China

[2]Chongqing Clinical Research Center for Reproductive Medicine, Chongqing Health Center for Women and Children, 400010, Chongqing, China

[3]Guangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, 510310, Guangzhou, China

关键词: Aged oocytes;    Growth hormone;    Aneuploidy;    Oocyte quality;    MAPK3/1;    JAK2;   

DOI  :  10.1186/s12967-023-04296-z

 received in 2023-04-03, accepted in 2023-06-22,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe global delay in women’s reproductive age has raised concerns about age-related infertility. The decline in oocyte quality is a limiting factor of female fertility, yet there are currently no strategies to preserve oocyte quality in aged women. Here, we investigated the effects of growth hormone (GH) supplementation on aneuploidy of aged oocytes.MethodsFor the in vivo experiments, the aged mice (8-month-old) were intraperitoneally injected with GH daily for 8 weeks. For the in vitro experiments, germinal vesicle oocytes from aged mice were treated with GH during oocyte maturation. The impacts of GH on ovarian reserve before superovulation was evaluated. Oocytes were retrieved to assess oocyte quality, aneuploidy and developmental potential characteristics. Quantitative proteomics analysis was applied to investigate the potential targets of GH in aged oocytes.ResultsIn this study, we demonstrated that GH supplementation in vivo not only alleviated the decline in oocyte number caused by aging, but also improved the quality and developmental potential of aged oocytes. Strikingly, we discovered that GH supplementation reduced aneuploidy in aged oocytes. Mechanically, in addition to improving mitochondrial function, our proteomic analysis indicated that the MAPK3/1 pathway may be involved in the reduction in aneuploidy of aged oocytes, as confirmed both in vivo and in vitro. In addition, JAK2 may also act as a mediator in how GH regulates MAPK3/1.ConclusionsIn conclusion, our research reveals that GH supplementation protects oocytes against aging-related aneuploidy and enhances the quality of aged oocytes, which has clinical significance for aged women undergoing assisted reproduction technology.Graphical Abstract

【 授权许可】

CC BY   
© The Author(s) 2023

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