Retinoic Acid Is Sufficient for the In Vitro Induction of Mouse Spermatocytes

Stem Cell Reports. 2016 Jul 12;7(1):80-94. doi: 10.1016/j.stemcr.2016.05.013. Epub 2016 Jun 23.

Abstract

Meiosis is the key step in gametogenesis. However, the mechanism of mammalian meiosis remains poorly understood due to the lack of an in vitro model. Here, we report that retinoic acid (RA) is sufficient for inducing leptotene/zygotene spermatocytes from cultured mouse spermatogonial stem cells. Multiple genes regulated by RA were identified by RNA sequencing. RA in combination with pup Sertoli cell co-culture resulted in a higher induction efficiency of 28%. Comparisons in the transcriptomic profiles of the induced spermatogenic cells and the isolated ones revealed the progressive induction of the germ cells. Using this model, we showed that Stra8, Agpat3, Fam57a, Wdr91, and Sox30 contributed to the proliferation and meiosis initiation differentially. In conclusion, we have efficiently generated spermatocytes using an RA/pup Sertoli cell-based in vitro model and provided proof-of-concept evidence for its application in identifying genes involved in mammalian meiosis.

Keywords: Sertoli cells; meiosis; retinoic acid; spermatocytes; spermatogonial stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects*
  • Coculture Techniques
  • Male
  • Meiosis / drug effects
  • Mice
  • Sertoli Cells / cytology
  • Sertoli Cells / drug effects
  • Spermatocytes / cytology
  • Spermatocytes / drug effects
  • Spermatogenesis / genetics
  • Spermatogonia / drug effects
  • Spermatogonia / growth & development*
  • Stem Cells / drug effects*
  • Tretinoin / administration & dosage*

Substances

  • Tretinoin