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Development. 2009 Jun;136(12):2091-100. doi: 10.1242/dev.020040.

Expression of retinoic acid receptor alpha in the germline is essential for proper cellular association and spermiogenesis during spermatogenesis.

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Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.


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.

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