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Ann. N.Y. Acad. Sci., Annals PrePrint, published online ahead of print September 28, 2007 doi: 10.1196/annals.1411.008 Copyright © 2007 by the New York Academy of Sciences description
1 School of Molecular Biosciences, Washington State University, Abelson 301, Pullman, Washington, 99164, United States 2 Department of Animal Sciences, Washington State University, Clark 116, Pullman, Washington, 99164, United States 3 School of Molecular Biosciences, Washington State University, Morrill 208, Pullman, Washington, 99164, United States
* To whom correspondence should be addressed. E-mail: khkim{at}wsu.edu. PrePrint Abstract
Elucidation of the retinoid signaling circuitry in the testis is critical to understanding how male germ cells develop to spermatozoa. 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 (Rara) knockout male mice. The seminiferous tubules of Rara knockout mice showed varying degrees of germ cell degeneration. A dramatic increase in apoptosis of early meiotic prophase spermatocytes was observed in these tubules compared to the wild-type tubules. Germ cell loss was dependent on the stages of the spermatogenic cycle: germ cell loss was negligible in stages I-V, 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-type donor germ cells, transplanted into Rara knockout testes, colonized and proliferated in the RARA-deficient microenvironment. The donor-derived cells were mostly early meiotic prophase spermatocytes, with few, more advanced germ cells detected. Conversely, when Rara-deficient germ cells were injected into the microenvironment that express RARA, establishment of donor-derived germ cell colonies was rare, but remarkably, once colonized, Rara-deficient 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. Key Words:
retinoids, testis, retinoic acid receptor A, vitamin A-deficiency, spermatogonial transplantation, epididymis
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