title: Retinol dehydrogenase 10 is indispensible for spermatogenesis in juvenile males.
abstract: Retinoic acid (RA), an active vitamin A derivative, is essential for mammalian spermatogenesis. Genetic studies have revealed that oxidation of vitamin A to retinal by retinol dehydrogenase 10 (RDH10) is critical for embryonic RA biosynthesis. However, physiological roles of RDH10 in postnatal RA synthesis remain unclear, given that Rdh10 loss-of-function mutations lead to early embryonic lethality. We conducted in vivo genetic studies of Rdh10 in postnatal mouse testes and found that an RDH10 deficiency in Sertoli cells, but not in germ cells, results in a mild germ cell depletion phenotype. A deficiency of RDH10 in both Sertoli and germ cells in juvenile mice results in a blockage of spermatogonial differentiation, similar to that seen in vitamin A-deficient animals. This defect in spermatogenesis arises from a complete deficiency in juvenile testicular RA synthesis and can be rescued by retinoid administration. Thus, in juvenile mice, the primary, but not exclusive, source of RA in the testes is Sertoli cells. In contrast, adult Rdh10-deficient mice exhibit phenotypically normal spermatogenesis, indicating that during development a change occurs in either the cellular source of RA or the retinaldehyde dehydrogenase involved in RA synthesis.
authors.affiliation: School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA. minghan@wsu.edu
authors.forename: Ming-Han
authors.initials: MH
authors.lastname: Tong
authors.forename: Qi-En
authors.initials: QE
authors.lastname: Yang
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Davis
authors.forename: Michael D
authors.initials: MD
authors.lastname: Griswold
mesh_terms: D000429:Alcohol Oxidoreductases / Q000172:deficiency / Q000378:metabolism*; D000818:Animals; D017931:DNA Primers / Q000235:genetics; D005697:Galactosides; D006652:Histological Techniques; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007211:Indoles; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012708:Sertoli Cells / Q000378:metabolism; D013091:Spermatogenesis / Q000502:physiology*; D013737:Testis / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism
chemical_list: D017931:DNA Primers; D005697:Galactosides; D007211:Indoles; D014801:Vitamin A; D014212:Tretinoin; D000429:Alcohol Oxidoreductases; C113992:trans-retinol dehydrogenase; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside