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Retinoic acid receptor A protein (RARA) is an essential mediator of retinoid signaling in the testis, as shown by a sterility phenotype observed for retinoic acid receptor A gene (<jats:italic>Rara<\/jats:italic>) knockout male mice. The seminiferous tubules of <jats:italic>Rara<\/jats:italic> knockout mice showed varying degrees of germ\u2010cell degeneration. A dramatic increase in apoptosis of early meiotic prophase spermatocytes was observed in these tubules compared to the wild\u2010type tubules. Germ\u2010cell loss was dependent on the stages of the spermatogenic cycle: germ\u2010cell loss was negligible in stages I\u2013V, but severe after stages VIII and IX of the spermatogenic cycle. Using spermatogonial transplantation, the individual function of RARA in Sertoli cells or germ cells was determined. The wild\u2010type donor germ cells, transplanted into <jats:italic>Rara<\/jats:italic> knockout testes, colonized and proliferated in the RARA\u2010deficient microenvironment. The donor\u2010derived cells were mostly early meiotic prophase spermatocytes, with few more advanced germ cells detected. Conversely, when <jats:italic>Rara<\/jats:italic>\u2010deficient germ cells were injected into the microenvironment that express RARA, establishment of donor\u2010derived germ\u2010cell colonies was rare, but remarkably, once colonized, <jats:italic>Rara<\/jats:italic>\u2010deficient germ cells progressed normally through spermatogenesis. These results together suggest that RARA may function in Sertoli cells to promote the survival and development of early meiotic prophase spermatocytes, whereas RARA in germ cells functions to increase the proliferation and differentiation of spermatogonia, prior to meiotic prophase.<\/jats:bold> <\/jats:p>","DOI":"10.1196\/annals.1411.008","type":"journal-article","created":{"date-parts":[[2008,1,9]],"date-time":"2008-01-09T21:02:44Z","timestamp":1199912564000},"page":"114-130","source":"Crossref","is-referenced-by-count":46,"title":["Potential Functions of Retinoic Acid Receptor A in Sertoli Cells and Germ Cells During Spermatogenesis"],"prefix":"10.1111","volume":"1120","author":[{"given":"TIMOTHY J.","family":"DOYLE","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KIRT W.","family":"BRAUN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DEREK 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