MECHANISMS OF TOXICITY IN TESTES

我们研究的目的是了解Hsp27在毒物引起的精子发生障碍中的作用。我们假设HSP27调节SC中的微丝(MFS)，毒物通过改变SC MFS而损害精子发生，其结果是影响生精上皮周期阶段HSP27表达和磷酸化的正常模式。具体地说，我们假设：1)转录因子HSF1和HSF2的变化控制着HSP27在精子发生过程中的表达，毒物可以改变HSF1和HSF2的激活和/或表达；2)HSP27的磷酸化亚型对MFS具有不同的影响，HSP27的亚型在SC中将有不同的定位；3)只有在分化的SC中表达的新蛋白介导HSP27对SC MFS的调节；以及4)在转基因动物SC中HSP27表达的选择性改变将导致与毒物引起的SC MF依赖事件的变化。

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.