MECHANISMS OF TOXICITY IN TESTES

我们研究的目的是了解hsp27在毒物诱导的精子发生破坏中的作用。我们假设hsp27调节SC中的微丝（MFs），毒物通过影响正常的hsp27表达模式和发生在精原上皮周期阶段的磷酸化，从而改变SC的微丝（MFs），从而损害精子发生。具体来说，我们假设：1)在精子发生过程中，转录因子HSF1和HSF2的变化控制着hsp27的表达，毒物会改变HSF1和HSF2的激活和/或表达，2)hsp27的磷酸化异构体对MFs有不同的影响，hsp27的异构体在SC中的定位也不同，3)一种仅由分化的SC表达的新蛋白介导了hsp27对SC MFs的调节。4)转基因动物SC中hsp27表达的选择性改变会导致SC中类似毒物引起的mf依赖性事件的改变。

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.