title: Processive pulses of retinoic acid propel asynchronous and continuous murine sperm production.
abstract: The asynchronous cyclic nature of spermatogenesis is essential for continual sperm production and is one of the hallmarks of mammalian male fertility. While various mRNA and protein localization studies have indirectly implicated changing retinoid levels along testis tubules, no quantitative evidence for these changes across the cycle of the seminiferous epithelium currently exists. This study utilized a unique mouse model of induced synchronous spermatogenesis, localization of the retinoid-signaling marker STRA8, and sensitive quantification of retinoic acid concentrations to determine whether there are fluctuations in retinoid levels at each of the individual stages of germ cell differentiation and maturation to sperm. These data show that processive pulses of retinoic acid are generated during spermatogonial differentiation and are the likely trigger for cyclic spermatogenesis and allow us, for the first time, to understand how the cycle of the seminiferous epithelium is generated and maintained. In addition, this study represents the first direct quantification of a retinoid gradient controlling cellular differentiation in a postnatal tissue.
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: University of Washington Medical Center, University of Washington, Seattle, Washington.
authors.forename: Samuel
authors.initials: S
authors.lastname: Arnold
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: University of Washington Medical Center, University of Washington, Seattle, Washington.
authors.forename: Nina
authors.initials: N
authors.lastname: Isoherranen
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; D008297:Male; D051379:Mice; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018168:Receptors, Retinoic Acid; C102019:Stra8 protein, mouse; D014212:Tretinoin
keywords: retinoic acid; spermatogenesis; spermatogonia; testis