Somatic cell-derived BMPs induce premature meiosis in male germ cells during the embryonic stage by upregulating Dazl expression

FASEB J. 2022 Feb;36(2):e22131. doi: 10.1096/fj.202101585R.

Abstract

Although germ cell fate is believed to be determined by signaling factors from differentiated somatic cells, the molecular mechanism behind this process remains obscure. In this study, premature meiosis in male germ cells was observed during the embryonic stage by conditional activation of β-catenin in Sertoli cells. Somatic and germ cell transcriptome results indicated that the BMP signaling pathway was enriched after β-catenin activation. In addition, we observed a decreased DNA methylation within a reduction of DNMT3A in germ cells of β-catenin activated testes and reversed increase after inhibiting BMP signaling pathway with LDN-193189. We also found that Dazl expression was increased in β-catenin activated testes and decreased after LDN treatment. Taken together, this study demonstrates that male germ cells entered meiosis prematurely during the embryonic stage after β-catenin activated in Sertoli cells. BMP signaling pathway involved in germ cell meiosis initiation by mediating DNA methylation to induce meiotic genes expression.

Keywords: Dazl; BMP signaling pathway; DNA methylation; meiosis initiation; β-catenin activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / genetics*
  • Cell Differentiation / genetics
  • DNA Methylation / genetics
  • Embryonic Development / genetics*
  • Female
  • Germ Cells / physiology*
  • Male
  • Meiosis / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Pregnancy
  • RNA-Binding Proteins / genetics*
  • Sertoli Cells / physiology
  • Signal Transduction / genetics
  • Testis / pathology
  • Transcriptome / genetics
  • Up-Regulation / genetics*
  • beta Catenin / genetics

Substances

  • Bone Morphogenetic Proteins
  • DAZL protein, mouse
  • RNA-Binding Proteins
  • beta Catenin