Exposure to retinoic acid in the neonatal but not adult mouse results in synchronous spermatogenesis

Elizabeth M. Snyder, Jeffrey C. Davis, Qing Zhou, Ryan Evanoff, Michael D. Griswold

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


Retinoic acid (RA) is required for germ cell differentiation, the regulation of which gives rise to a constant production of mature sperm. In testes from 3-day postpartum (dpp) RARE-hsplacZ mice, periodic regions positive for beta-galactosidase activity were observed along the length of the seminiferous tubules. Periodicity was abolished by treatment of neonates with exogenous RA at 2 dpp. To assess the consequences, 2-dpp mice were treated with RA, and the long- and short-term effects were assessed. Long-term effects of neonatal RA exposure included a delay in the appearance of advanced germ cells and the absence of a spermatogenic wave (synchronous spermatogenesis) in the adult. In contrast, RA exposure in vitamin Asufficient adults did not result in synchronous spermatogenesis but rather induced apoptosis in a subset of spermatogonia. Shortly after (24 h) neonates were exposed, altered expression of known germ cell differentiation and the (Stra8, Kit, Sycp3, and Rec8) meiosis markers and an increase in the number of STRA8 and SYCP3 immunopositive cells were observed relative to those of vehicle controls. However, 48 and 72 h after exposure, a significant reduction in the number of STRA8 and SYCP3 immunopositive cells occurred. Immunohistochemical analysis of a marker for apoptosis demonstrated neonatal exposure resulted in increased germ cell apoptosis, as observed in the adult. Additionally, RA exposure resulted in increased Cyp26a1 expression of the RA-degrading enzyme. Thus, while RA treatment of neonatal and adult mice resulted in apoptosis of spermatogonia, synchronous spermatogenesis occurred only after neonatal RA exposure.

Original languageEnglish (US)
Pages (from-to)886-893
Number of pages8
JournalBiology of reproduction
Issue number5
StatePublished - May 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Cell Biology


  • Apoptosis
  • Gametogenesis
  • Germ cell differentiation
  • Retinoic acid
  • Spermatogenesis
  • Testis
  • Vitamin A deficiency


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