Retinoic acid availability drives the asynchronous initiation of spermatogonial differentiation in the mouse

Elizabeth M. Snyder, Christopher Small, Michael D. Griswold

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

Throughout the reproductive lifespan of most male mammals, sperm production is constant because of the regulated differentiation of spermatogonia. Retinoic acid (RA) and a downstream target, Stra8, are required for complete spermatogenesis. To examine the role of RA in initiating spermatogonial differentiation, a transgenic mouse model expressing beta-galactosidase under the control of an RA response element was used. Cells in the neonatal testis undergoing active RA signaling were visualized by beta-galactosidase activity, the relationship between RA and differentiation determined, and the role of RA-degrading enzymes in regulating RA demonstrated. Betagalactosidase activity was found to be predominantly associated with differentiating, premeiotic germ cells and to be distributed nonuniformly throughout the seminiferous tubules. Additionally, beta-galactosidase activity in premeiotic germ cells colocalized with STRA8 protein and was induced in germ cells with exogenous RA treatment. The RA-degrading enzyme, CYP26B1, was found to have germ cell localization and nonuniform distribution between tubules via immunohistochemistry. Treatment with a CYP26 enzyme inhibitor resulted in an increased number of germ cells with both beta-galactosidase activity and STRA8 protein and an increase in the expression of genes associated with differentiation and reduced expression of a gene associated with undifferentiated germ cells. These results show the action of RA in a subset of spermatogonia leads to nonuniform initiation of differentiation throughout the neonatal testis, potentially mediated through the action of CYP26 enzymes. Thus, the presence of RA is a likely driving factor in the initiation of spermatogonial differentiation and may result in asynchronous spermatogenesis.

Original languageEnglish (US)
Pages (from-to)783-790
Number of pages8
JournalBiology of reproduction
Volume83
Issue number5
DOIs
StatePublished - Nov 1 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Cell Biology

Keywords

  • CYP26
  • Gametogenesis
  • Germ cell differentiation
  • Retinoic acid
  • Spermatogenesis
  • Spermatogonia
  • Testis

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