Retinoic acid combined with spermatogonial stem cell conditions facilitate the generation of mouse germ-like cells

Biosci Rep. 2017 Apr 20;37(2):BSR20170637. doi: 10.1042/BSR20170637. Print 2017 Apr 30.


Spermatogenic lineage has been directly generated in spermatogonial stem cell (SSC) conditions from human pluripotent stem cells (PSCs). However, it remains unknown whether mouse embryonic stem cells (ESCs) can directly differentiate into advanced male germ cell lineage in the same conditions. Here, we showed rather low efficiency of germ-like cell generation from mouse ESCs in SSC conditions. Interestingly, addition of retinoic acid (RA) into SSC conditions enabled efficient differentiation of mouse ESCs into germ-like cells, as shown by the activation of spermatogenesis-associated genes such as Mvh, Dazl, Prdm14, Stella, Scp1, Scp3, Stra8 and Rec8 In contrast, for cells cultured in control medium, the activation of the above genes barely occurred. In addition, RA with SSC conditions yielded colonies of Acrosin-expressing cells and the positive ratio reached a peak at day 6. Our work thus establishes a simple and cost-efficient approach for male germ like cell differentiation from mouse PSCs and may propose a useful strategy for studying spermatogenesis in vitro.

Keywords: Differentiation; Germ-like cells; Retinoic acid; Spermatogonial stem cell conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Adult Germline Stem Cells / physiology*
  • Animals
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Germ Cells / physiology*
  • Humans
  • Male
  • Mice
  • Spermatogenesis / physiology
  • Stem Cells / physiology*
  • Tretinoin / pharmacology*


  • Tretinoin