Growth hormone reduces aneuploidy and improves oocytes quality by JAK2-ERK1/2 pathway in aging mice

Abstract

Abstract Background The 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; however, strategies to maintain the oocyte quality of aging women are not available. Here, we investigated the effects of growth hormone (GH) supplementation on aneuploidy of aging oocytes.Methods For the in vivo experiments, the aging mice (8-month-old) were intraperitoneally injected with GH every day for 8 weeks. For the in vitro experiments, germinal vesicle oocytes from aging mice were treated with GH. The impacts of GH on ovarian reserve before superovulation was evaluated. Oocytes were retrieved to determine oocyte quality, aneuploidy and developmental potential parameters. Quantitative proteomics analysis was applied to investigate the potential targets of GH in aging oocytes.Results In this study, we showed 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 aging oocytes. Strikingly, we found that GH supplementation reduced aneuploidy in aging oocytes. Mechanically, in addition to improving mitochondrial function, our proteomic analysis indicated that the ERK1/2 pathway might be involved in the reduction in aneuploidy of aging oocytes, as confirmed both in vivo and in vitro. In addition, JAK2 might mediate the regulation of ERK1/2 by GH.Conclusions In summary, our findings reveal that GH supplementation protects oocytes from aging-related aneuploidy and enhances the quality of aging oocytes, which has clinical implications in assisted reproduction of aging women.