Diethylstilbestrol and uterine development

描述(由申请人提供) 化学毒物通过干扰我们的正常生理来影响我们的身体功能，己烯雌酚(DES)是一类对第二代人的福祉具有毁灭性影响的雌激素化合物。以前是在孕妇身上，她们的胎儿从1947年到1971年接触到DES，导致了一系列的发育 包括癌症在内的女性和男性生殖道的异常。最近，DES的作用模式被认为涉及关键发育时期的几个重要发育基因的抑制，包括Hox，Wnt，Insulin-3。我们的长期目标是研究控制生殖道发育的基因途径以及如何 外生因素可以影响这一过程。在这项应用中，我们首先提出使用最先进的Affymetrix基因阵列技术来鼓励其表达被DES改变的基因。其次，我们将检查这些候选基因中是否有任何一个在Hoxa10和Hoxa11的下游发挥功能，因为这两个基因在早期生殖道发育中的功能是通过敲除小鼠揭示的。这项研究收集的信息将对DES致畸和正常子宫发育的研究都有价值。

Description (provided by applicant) Chemical toxicants affect our body function by interfering with our normal physiology, diethylstilbestrol (DES) represents a class of estrogenic compounds that had devastating effects on the well-being of these second generation. It was formerly in pregnant women and their fetuses were exposed to DES from 1947 to 1971 resulting in a spectrum of developmental abnormalities in both the female and the male reproductive tracts including cancer. The mode of DES action has recently been suggested to involve the repression of several developmentally important genes including Hox, Wnt, insulin-3 during critical developmental periods. Our long term goal is to study the genic pathway controlling reproductive tract development and how exogenous factors can influence the process. In this application we first propose to use the state of the art Affymetrix gene-array technology to encourage genes whose expression is altered by DES. Second, we will examine whether any of these candidate genes functions downstream of Hoxa10 and Hoxa11, as the function of these two genes in earlier reproductive tract development was revealed by knock-out mice. Information gathered from this study will be valuable both in the study of DES teratogenicity and normal uterine development.