Retinoic acid induces multiple hallmarks of the prospermatogonia-to-spermatogonia transition in the neonatal mouse.
In mammals, most neonatal male germ cells (prospermatogonia) are quiescent and located in the center of the testis cords. In response to an unknown signal, prospermatogonia transition into spermatogonia, reenter the cell cycle, divide, and move to the periphery of the testis cords. In mice, these events occur by 3-4 days postpartum (dpp), which temporally coincides with the onset of retinoic acid (RA) signaling in the neonatal testis. RA has a pivotal role in initiating germ cell entry into meiosis in both sexes, yet little is known about the mechanisms and about cellular changes downstream of RA signaling. We examined the role of RA in mediating the prospermatogonia-to-spermatogonia transition in vivo and found 24 h of precocious RA exposure-induced germ cell changes mimicking those that occur during the endogenous transition at 3-4 dpp. These changes included: 1) spermatogonia proliferation; 2) maturation of cellular organelles; and 3), expression of markers characteristic of differentiating spermatogonia. We found that germ cell exposure to RA did not lead to cellular loss from apoptosis but rather resulted in a delay of ∼2 days in their entry into meiosis. Taken together, our results indicate that exogenous RA induces multiple hallmarks of the transition of prospermatogonia to spermatogonia prior to their entry into meiosis.
Department of Anatomy and Cell Biology, Brody School of Medicine at East Carolina University, Greenville, North Carolina.
Jonathan T
JT
Busada
Evelyn P
EP
Kaye
Randall H
RH
Renegar
Christopher B
CB
Geyer
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics; D019084:Fluorescent Antibody Technique, Indirect; D006056:Golgi Apparatus / Q000187:drug effects; D008297:Male; D008540:Meiosis / Q000187:drug effects; D051379:Mice; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects; D015388:Organelles / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D000072516:Retinoic Acid 4-Hydroxylase; D013076:Sperm Count; D013079:Sperm Maturation / Q000187:drug effects*; D013091:Spermatogenesis; D013093:Spermatogonia / Q000187:drug effects*; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D016707:Tissue Fixation; D014212:Tretinoin / Q000494:pharmacology*
D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; C102019:Stra8 protein, mouse; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase
developmental biology; gamete biology; retinoids; spermatogonia; testis