In the new grant period we will utilize the information we have extracted from our large microarray databasesto focus on the process of spermatogonial maturation and the role of retinoids in that process. Our array dataclearly identifies a retinoid responsive gene, termed StraS, that is expressed in germ cells of the postnatalmale and embryonic female as a precursor to entry into meiosis. Previous work in our laboratory and otherlaboratories has shown that a vitamin A deficiency blocks the conversion of undifferentiated spermatogoniato differentiating A1 spermatogonia. This observation suggests retinoic acid is required for theundifferentiated spermatogonia to enter into a differentiation pathway and ultimately into meiosis. Inductionof the gene, StraS, is a requirement and a reliable marker for this process. The action of retinoic acid andthe subsequent changes in gene expression that occur, dramatically impact the maturation of spermatogoniaand the onset of meiosis. Major parts of the proposed project are to more clearly define the response ofspermatogonia to retinoic acid, to examine the response of the StraS gene in detail and to find other genesinvolved in the maturation process. In particular, we will focus on the potential role of 3 additional genes,Tex13, Xlr4 and an EST no. 1700013H16Rik which all share a pattern of expression that mirrors that ofStraS.
Three specific aims are proposed: 1. Define the retinoic acid response of the testis with regard to thesomatic cells and the maturation of spermatogonia. 2. Define the transcriptional elements that regulate StraSexpression and spermatogonial maturation. 3. Determine the cellular localization and direct interactingpartners of StraS, Tex13, Xlr4 and 1700013H16Rik in spermatocytes. This research project couldpotentially determine the molecular mechanisms that initiate spermatogenesis in the male germline.Knowledge about the actions of retinoic acid and the genes responsible for the entry of spermatogonia intothe differentiation pathway could lead to new approaches to contraception.
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