Diethylstilbestrol and uterine development

己烯雌酚与子宫发育

• 批准号: 6492427
• 负责人: Liang Ma
• 金额: $ 14.85万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-05 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6492427
• 关键词: biological signal transduction; diethylstilbestrol; female; gene expression; growth factor; homeobox genes; in situ hybridization; laboratory mouse; microarray technology; newborn animals; polymerase chain reaction; reproductive development; toxin; transcription factor; uterus

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.

描述（由申请人提供） 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) 代表了一类雌激素化合物，对第二代的健康产生了毁灭性影响。它以前发生在孕妇中，她们的胎儿在 1947 年至 1971 年间暴露于 DES，导致一系列发育障碍。 女性和男性生殖道异常，包括癌症。最近有人提出，DES 的作用模式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 外源因素可以影响该过程。在此应用中，我们首先建议使用最先进的 Affymetrix 基因阵列技术来鼓励通过 DES 改变表达的基因。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 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通过敲除小鼠揭示。本研究收集的信息对于 DES 致畸性和正常子宫发育的研究都很有价值。