Primordial follicle activation is affected by the absence of Sohlh1 in mice

Mol Reprod Dev. 2019 Jan;86(1):20-31. doi: 10.1002/mrd.23078. Epub 2018 Nov 23.

Abstract

Previous studies have reported that only primordial follicles and empty follicles can be found in 7.5 days postparturition (dpp) Sohlh1-/- mouse ovaries and females are infertility. There appears to be a defect in follicle development during the primordial-to-primary follicle transition in Sohlh1-/- mouse ovaries. However, detailed analyses of these phenomena have not been performed. In this study, we used Sohlh1-/- transgenic mice to explore the role of Sohlh1 in folliculogenesis. The results showed that only primordial follicles and empty follicles can be observed in Sohlh1-/- ovaries from 0.5 to 23.5 dpp. The expression of Foxo3 and FOXO3 was downregulated; nucleocytoplasmic shuttling of FOXO3 was normal in 7.5-dpp Sohlh1+/+ but not Sohlh1-/- ovaries; and primordial follicle activation (PFA) was not observed in 7.5-dpp Sohlh1-/- mice. The expression levels of KIT, AKT, and P308-AKT were downregulated (p < 0.05), whereas that of P473-AKT was not significantly changed (p > 0.05). The KIT/PI3K/AKT pathway was inhibited. Furthermore, we conducted a dual luciferase assay and chromatin immunoprecipitation. The results showed that SOHLH1 can upregulate the Kit gene by binding to the -3698 bp E-box motif. The absence of Sohlh1 may affect PFA in mouse ovaries via downregulation of Kit and inhibition of the KIT/PI3K/AKT pathway.

Keywords: AKT; KIT; PI3K; Sohlh1; primordial follicle activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Female
  • Forkhead Box Protein O3 / genetics
  • Forkhead Box Protein O3 / metabolism
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Knockout
  • Ovarian Follicle / growth & development*
  • Proto-Oncogene Proteins c-kit / biosynthesis
  • Proto-Oncogene Proteins c-kit / genetics
  • Response Elements
  • Signal Transduction*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Forkhead Box Protein O3
  • FoxO3 protein, mouse
  • Kit protein, mouse
  • Sohlh1 protein, mouse
  • Proto-Oncogene Proteins c-kit