title: CYP26 Enzymes Are Necessary Within the Postnatal Seminiferous Epithelium for Normal Murine Spermatogenesis.
abstract: The active metabolite of vitamin A, retinoic acid (RA), is known to be essential for spermatogenesis. Changes to RA levels within the seminiferous epithelium can alter the development of male germ cells, including blocking their differentiation completely. Excess RA has been shown to cause germ cell death in both neonatal and adult animals, yet the cells capable of degrading RA within the testis have yet to be investigated. One previous study alluded to a requirement for one of the RA degrading enzymes, CYP26B1, in Sertoli cells but no data exist to determine whether germ cells possess the ability to degrade RA. To bridge this gap, the roles of CYP26A1 and CYP26B1 within the seminiferous epithelium were investigated by creating single and dual conditional knockouts of these enzymes in either Sertoli or germ cells. Analysis of these knockout models revealed that deletion of both Cyp26a1 and Cyp26b1 in either cell type resulted in increased vacuolization within the seminiferous tubules, delayed spermatid release, and an increase in the number of STRA8-positive spermatogonia, but spermatozoa were still produced and the animals were found to be fertile. However, elimination of CYP26B1 activity within both germ and Sertoli cells resulted in severe male subfertility, with a loss of advanced germ cells from the seminiferous epithelium. These data indicate that CYP26 activity within either Sertoli or germ cells is essential for the normal progression of spermatogenesis and that its loss can result in reduced male fertility.
authors.affiliation: School of Molecular Biosciences and the Center for Reproductive Biology, Washington State University, Pullman, Washington.
authors.forename: Cathryn A
authors.initials: CA
authors.lastname: Hogarth
authors.affiliation: School of Molecular Biosciences and the Center for Reproductive Biology, Washington State University, Pullman, Washington.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Evans
authors.affiliation: School of Molecular Biosciences and the Center for Reproductive Biology, Washington State University, Pullman, Washington.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Onken
authors.affiliation: School of Molecular Biosciences and the Center for Reproductive Biology, Washington State University, Pullman, Washington.
authors.forename: Travis
authors.initials: T
authors.lastname: Kent
authors.affiliation: School of Molecular Biosciences and the Center for Reproductive Biology, Washington State University, Pullman, Washington.
authors.forename: Debra
authors.initials: D
authors.lastname: Mitchell
authors.affiliation: Cancer Research Institute, Queen's University, Kingston Ontario, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Petkovich
authors.affiliation: School of Molecular Biosciences and the Center for Reproductive Biology, Washington State University, Pullman, Washington mgriswold@vetmed.wsu.edu.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Griswold
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D005854:Germ Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000072516:Retinoic Acid 4-Hydroxylase; D012670:Seminiferous Epithelium / Q000201:enzymology*; D012708:Sertoli Cells / Q000378:metabolism; D013091:Spermatogenesis / Q000502:physiology*; D013093:Spermatogonia / Q000378:metabolism; D013094:Spermatozoa / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C102019:Stra8 protein, mouse; D003577:Cytochrome P-450 Enzyme System; C000607080:Cyp26a1 protein, mouse; C000607081:Cyp26b1 protein, mouse; D000072516:Retinoic Acid 4-Hydroxylase
keywords: CYP26; Sertoli cells; retinoic acid; spermatogenesis; testis