Journal article
Retinoic acid availability drives the asynchronous initiation of spermatogonial differentiation in the mouse
Biology of reproduction, Vol.83(5), pp.783-790
11/2010
Handle:
https://hdl.handle.net/2376/104057
PMID: 20650878
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. Beta-galactosidase 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.
Metrics
7 Record Views
Details
- Title
- Retinoic acid availability drives the asynchronous initiation of spermatogonial differentiation in the mouse
- Creators
- Elizabeth M Snyder - School of Molecular Biosciences, Washington State University, Pullman, Washington 99164, USAChristopher SmallMichael D Griswold
- Publication Details
- Biology of reproduction, Vol.83(5), pp.783-790
- Academic Unit
- Molecular Biosciences, School of
- Publisher
- United States
- Grant note
- U54 HD042454-06 / NICHD NIH HHS U54 HD042454 / NICHD NIH HHS R37 HD010808 / NICHD NIH HHS R01 HD010808 / NICHD NIH HHS R01 HD010808-32 / NICHD NIH HHS HD10808 / NICHD NIH HHS
- Identifiers
- 99900546609401842
- Language
- English
- Resource Type
- Journal article