Expression of retinoic acid receptor alpha in the germline is essential for proper cellular association and spermiogenesis during spermatogenesis.
Signaling through vitamin A metabolites is indispensable for spermatogenesis, and disruption of retinoic acid receptor alpha (RARalpha) function resulted in male sterility and aberrant spermatogenesis, which resembled vitamin A deficiency. Here we investigated the lineage- and cell-specific role of RARalpha-mediated signaling during spermatogenesis using germ-cell transplantation and genetically manipulated mouse models. We demonstrated that RARalpha-deficient germ-cell stem cells were able to repopulate germ-cell-depleted wild-type testes and initiate spermatogenesis; however, improper cellular associations and abnormal sperm formation were observed. We further generated RARalpha-deficient mice that expressed RARalpha-EGFP fusion protein uniquely in haploid germ cells. Strikingly, spermatid orientation, alignment and release, as well as sperm morphology, were normal and there was a partial rescue of sterility. These data provide the first direct evidence for a distinct requirement of RARalpha-mediated retinoid signaling specifically in germ cells.
Chung
Sanny S W
SS
Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
Wang
Xiangyuan
X
Wolgemuth
Debra J
DJ
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D008297:Male; D051379:Mice; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis*; D000072482:Retinoic Acid Receptor alpha; D015398:Signal Transduction; D013091:Spermatogenesis / Q000502:physiology*; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013737:Testis / Q000166:cytology
C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha