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THE EFFECTS OF HYPERTHERMIA ON SPERMATOGENESIS, APOPTOSIS, GENE EXPRESSION AND FERTILITY IN ADULT MALE MICE
Citation:
Rockett, J C., F. L. Mapp, J B. Garges, J. C. Luft, C. Mori, AND D J. Dix. THE EFFECTS OF HYPERTHERMIA ON SPERMATOGENESIS, APOPTOSIS, GENE EXPRESSION AND FERTILITY IN ADULT MALE MICE. Presented at Triangle Consortium for Reproductive Biology, RTP, NC, January 27, 2001.
Description:
The effects of hyperthermia on spermatogenesis, apoptosis, gene expression and fertility in adult male mice
John C. Rockett1, Faye L. Mapp1, J. Brian Garges1, J. Christopher Luft1, Chisato Mori2 and David J. Dix1.
1Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 and 2 Department of Anatomy, School of Medicine, Chiba University, Chiba 260-8670, Japan, and Core Research for Evolutional Science and Technology CREST, Kawaguchi City, Saitama 332-0012, Japan.
Abstract
A well-characterized mouse model of temporary infertility, testicular heat shock, was used to further characterize the cellular and molecular mechanisms that may be involved in environmentally induced male infertility. This model is pertinent because heat shock proteins (HSPs), induced by heat shock, are required both in spermatogenesis and in protecting cells from the cytotoxic effects of such environmental hazards as heat, radiation and chemicals. Thus, perturbation of temporal or spatial HSP expression in the testis by exposure to such hazards may negatively impact sperm production. A variety of cellular and molecular methods, including histological analysis, immunohistochemistry, Western blot, TUNEL, RT-PCR and DNA microarrays, were used to characterize the effects of a single testicular heat shock (43?C for 20 minutes) at different times following treatment. A 10-week mating study following heat shock reaffirmed previous studies reporting that spermatocytes are the most susceptible subpopulation. Hyperthermia transiently disrupted spermatogenesis, resulting in spermatocytes with pyknotic nuclei and apoptotic bodies. Apoptosis in spermatocytes was identified by TUNEL as soon as 8h after treatment, and correlated with the expression of inducible HSP70-1/-3 protein. RT-PCR corroborated these cellular observations for HSP70s, and DNA arrays identified a larger network of genes with altered expression, including some which are known to be involved in apoptosis and stress. The observed changes suggest that genes such as Bag-1 and Bax are involved in the apoptotic mechanism, and implicate as many as six different families of HSPs and chaperonins in heat shock-induced infertility. (This is an abstract of a proposed presentation and does not necessarily reflect EPA policy)