Diethylstilbestrol and uterine development

说明（申请人提供） 化学毒物通过干扰我们的正常生理机能来影响我们的身体功能，己烯雌酚（DES）代表了一类对这些第二代人的健康产生破坏性影响的雌激素化合物。它以前是在孕妇和他们的胎儿暴露于DES从1947年至1971年，导致一系列的发展， 女性和男性生殖道的异常，包括癌症。DES的作用模式最近被认为涉及在关键发育时期抑制几个发育重要基因，包括Hox、Wnt、胰岛素-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控制生殖道发育。 外部因素会影响这一进程。在本申请中，我们首先建议使用最先进的Affymetrix基因阵列技术来激励其表达被DES改变的基因。其次，我们将研究这些候选基因中是否有任何一个在Hoxa 10和Hoxa 11的下游发挥作用，因为这两个基因在早期生殖道发育中的功能已被敲除小鼠揭示。从本研究中收集的信息将在DES致畸性和正常子宫发育的研究中有价值。

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.