title: Characterizing the Spermatogonial Response to Retinoic Acid During the Onset of Spermatogenesis and Following Synchronization in the Neonatal Mouse Testis.
abstract: Retinoic acid (RA), the active metabolite of vitamin A, is known to be required for the differentiation of spermatogonia. The first round of spermatogenesis initiates in response to RA and occurs in patches along the length of the seminiferous tubule. However, very little is known about the individual differentiating spermatogonial populations and their progression through the cell cycle due to the heterogeneous nature of the onset of spermatogenesis. In this study, we utilized WIN 18,446 and RA as tools to generate testes enriched with different populations of spermatogonia to further investigate 1) the undifferentiated to differentiating spermatogonial transition, 2) the progression of the differentiating spermatogonia through the cell cycle, and 3) Sertoli cell number in response to altered RA levels. WIN 18,446/RA-treated neonatal mice were used to determine when synchronous S phases occurred in the differentiating spermatogonial population following treatment. Five differentiating spermatogonial S phase windows were identified between spermatogonial differentiation and formation of preleptotene spermatocytes. In addition, a slight increase in Sertoli cell number was observed following RA treatment, possibly implicating a role for RA in Sertoli cell cycle progression. This study has enhanced our understanding of the spermatogonial populations present in the neonatal testis during the onset of spermatogenesis by mapping the cell cycle kinetics of both the undifferentiated and the differentiating spermatogonial populations and identifying the precise timing of when specific individual differentiating spermatogonial populations are enriched within the testis following synchrony, thus providing an essential tool for further study of the differentiating spermatogonia.
authors.affiliation: School of Molecular Biosciences and the Center for Reproductive Biology, Washington State University, Pullman, Washington.
authors.forename: Kellie S
authors.initials: KS
authors.lastname: Agrimson
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: Debra
authors.initials: D
authors.lastname: Mitchell
authors.affiliation: School of Molecular Biosciences and the Center for Reproductive Biology, Washington State University, Pullman, Washington.
authors.forename: Traci B
authors.initials: TB
authors.lastname: Topping
authors.affiliation: Laboratory of Structural Biology and Reproduction, Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Pampulha, Belo Horizonte, MG, Brazil.
authors.forename: Hélio
authors.initials: H
authors.lastname: Chiarini-Garcia
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 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; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D003959:Diamines / Q000494:pharmacology; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000378:metabolism; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D012671:Seminiferous Tubules / Q000378:metabolism; D012708:Sertoli Cells / Q000166:cytology / Q000187:drug effects; D015398:Signal Transduction; D013091:Spermatogenesis / Q000187:drug effects* / Q000502:physiology; D013093:Spermatogonia / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology* / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D003959:Diamines; C494988:Gfra1 protein, mouse; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; C102019:Stra8 protein, mouse; C002491:N,N'-bis(dichloroacetyl)-1,8-octamethylenediamine; D014212:Tretinoin
keywords: cell cycle; retinoic acid; spermatogenesis; spermatogonia; testis