Androgen Indirectly Regulates Gap Junction Component Connexin 43 Through Wilms Tumor-1 in Sertoli Cells

Stem Cells Dev. 2020 Feb 1;29(3):169-176. doi: 10.1089/scd.2019.0166. Epub 2020 Jan 13.

Abstract

In mammals, spermatogenesis is closely related to intercellular interactions of germ cells and surrounding Sertoli cells, that is, blood-testis barrier and gap junction, which are subjected to hormone signals in testicular seminiferous tubules. Androgen signal plays pivotal role in regulating spermatogenesis, but the underlying mechanism is largely unknown. Our recent study demonstrated a novel regulatory pattern of androgen in regulation of spermatogonia differentiation, in which androgen indirectly regulates the expression of ITGB1 on Sertoli Cells through intermediate molecule Wilms tumor-1 (Wt-1) during spermatogenesis. In this study, we identified that Connexin 43 (Cx43), the key component for gap junction distributed between spermatogonia and Sertoli cells, was also regulated by androgen signal. Chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR) demonstrated that WT1 occupied Cx43 promoter in Sertoli cells, suggesting WT1 as an intermediate molecule in regulation of Cx43. Finally, we revealed a regulatory pattern of Cx43 by androgen in Sertoli cells, and the Sertoli cells in germ cell depleted microenvironment were sensitive to androgen signal, which enhances the understanding of the mechanism of spermatogenesis.

Keywords: ChIP-qPCR; cellular interaction; gap junction; niche; signal pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / pharmacology*
  • Animals
  • Cells, Cultured
  • Connexin 43 / metabolism*
  • Male
  • Mice
  • Sertoli Cells / cytology
  • Sertoli Cells / drug effects*
  • Sertoli Cells / metabolism
  • Spermatogenesis
  • WT1 Proteins / metabolism

Substances

  • Androgens
  • Connexin 43
  • WT1 Proteins
  • WT1 protein, mouse