The purpose of our studies is to understand the role of hsp27 in toxicant-induced disruption of spermatogenesis. We hypothesize that hsp27 regulates microfilaments (MFs) in SC and that toxicants damage spermatogenesis by altering SC MFs as a consequence of affecting the normal pattern of hsp27 expression and phosphorylation occurring during the stages of the cycle of the seminiferous epithelium. Specifically we hypothesize: 1) that variations in transcription factors HSF1 and HSF2 control expression of hsp27 during spermatogenesis and that toxicants alter HSF1 and HSF2 activation and/or expression, 2) that phosphorylation isoforms of hsp27 exhibit differential effects on MFs and that the isoforms of hsp27 will localize differently in SC, 3) that a novel protein expressed only by differentiated SC mediates hsp27 regulation of SC MFs, and 4) that selective alteration of hsp27 expression in SC of transgenic animals will result in changes in SC MF- dependent events like those caused by toxicants.
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