MECHANISMS OF TOXICITY IN TESTES

本研究的目的是了解热休克蛋白27在毒物诱导的精子发生障碍中的作用。 我们推测，热休克蛋白27调节微丝（MF）在SC和毒物损害精子发生通过改变SC MF的结果，影响正常模式的热休克蛋白27的表达和磷酸化过程中发生的生精上皮细胞周期的阶段。 具体来说，我们假设：1）转录因子HSF 1和HSF 2的变化控制精子发生过程中hsp 27的表达，毒物改变HSF 1和HSF 2的活化和/或表达，2）hsp 27的磷酸化亚型对MF表现出不同的作用，hsp 27的亚型在SC中的定位不同，3）仅由分化的SC表达的新蛋白介导hsp 27对SC MFs的调节，和4）转基因动物SC中hsp 27表达的选择性改变将导致SC MF的变化。依赖性事件，如毒物引起的事件。

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.