Growth hormone ameliorates the age-associated depletion of ovarian reserve and decline of oocyte quality via inhibiting the activation of Fos and Jun signaling

Aging (Albany NY). 2021 Feb 17;13(5):6765-6781. doi: 10.18632/aging.202534. Epub 2021 Feb 17.

Abstract

Oocyte quality typically begins to decline with aging, which contributes to subfertility and infertility. However, there is still no effective treatment to restore the ovarian reserve and improve aged-oocyte quality. According to the present study, growth hormone (GH) secretion changes with maternal age in female mice. After intraperitoneal injection with GH (1 mg/kg body weight) every two days for two months, the 10-month-old mice showed a better ovarian reserve and oocyte quality than control mice. GH treatment decreased the occurrence rate of aneuploidy caused by spindle/chromosome defects. Additionally, the single oocyte transcriptome analysis indicated that GH decreased the expression of apoptosis-related genes in oocytes. It was also observed that GH treatment reduced the expression of γH2AX and apoptosis of aged oocytes via decreasing the activation of Fos and Jun. Collectively, our results indicate that GH treatment is an effective way to reverse the age-associated depletion of ovarian reserve and the decline of oocyte quality by decreasing apoptosis.

Keywords: aging; apoptosis; growth hormone; meiosis; oocyte quality.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Aneuploidy
  • Animals
  • Apoptosis / drug effects
  • Female
  • Gene Expression Profiling
  • Growth Hormone / pharmacology*
  • Histones / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Oocytes / drug effects
  • Oocytes / pathology
  • Ovarian Reserve / drug effects*
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Signal Transduction / drug effects

Substances

  • FOS protein, human
  • Histones
  • JUN protein, human
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • gamma-H2AX protein, mouse
  • Growth Hormone