Meiotic Studies of Chemicals With Estrogenic Activity

具有雌激素活性的化学物质的减数分裂研究

• 批准号: 8462603
• 负责人: Patricia Hunt
• 金额: $ 50.41万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-06 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8462603
• 关键词: Address; Adult; Affect; Amniotic Fluid; Aneuploidy; Blood; Chemicals; Chromosome Pairing; Chromosomes; Congenital Abnormality; Data; Embryo; Employee Strikes; Endocrine Disruptors; Environmental Risk Factor; Estrogen Receptors; Etiology; Event; Exposure to; Failure; Female; Fertility; Fetal Development; Fetus; Frequencies; Gametogenesis; Gene Expression; Genes; Genetic; Genetic Nondisjunction; Genetic Polymorphism; Genetic Variation; Genotype; Germ Cells; Homologous Gene; Hormones; Human; Knock-out; Laboratories; Longevity; Meiosis; Metabolism; Molecular; Mus; Oocytes; Oogenesis; Ovarian; Ovary; Perinatal Exposure; Play; Pregnancy; Pregnancy Tests; Pregnant Women; Production; Reproductive Health; Risk; Role; Serum; Staging; Termination of pregnancy; Testing; Time; Tissues; Translating; Variant; Woman; base; bisphenol A; chromosome movement; comparative; egg; estrogenic activity; fetal; in utero; member; mouse model; population based; prenatal exposure; public health relevance; reproductive; response

DESCRIPTION (provided by applicant): Aneuploidy, the loss or gain of chromosomes, is the leading cause of human pregnancy failure and birth defects. Most aneuploidy arises from maternal nondisjunction, but its etiology remains obscure. Environmental factors have long been suspected to play a role but, until recently, this has not been substantiated by direct evidence. Recent studies in our laboratory suggest that exposure to the estrogenic chemical, bisphenol A (BPA) during pregnancy dramatically increases the frequency of chromosomally abnormal eggs and embryos in the mouse. Because humans are exposed to BPA on a daily basis, these findings have serious implications for human reproductive health. The studies outlined in this application will use mouse models to test the effects of fetal BPA exposure on reproductive lifespan in the female and examine the mechanisms by which BPA exerts its effects on the early stages of oogenesis. In addition, we will translate our findings from mice to humans by directly studying human fetal oocytes to determine if BPA similarly impacts early oogenesis in humans. Lastly, we will test the effect of genetic variation on the ability of biologically active BPA to reach specific tissues and on the tissue response to BPA. The combined data from these studies will enhance our understanding of the risk to human fertility posed by this chemical.

描述（由申请人提供）：非整倍性（染色体的损失或增益）是人类妊娠失败和先天缺陷的主要原因。大多数非整倍性来自母体非分离，但其病因仍然晦涩难懂。长期以来，人们一直怀疑环境因素发挥作用，但直到最近，这还没有得到直接证据的证实。我们实验室的最新研究表明，妊娠期间暴露于雌激素化学物质A（BPA）会大大增加小鼠染色体异常卵和胚胎的频率。由于人类每天都暴露于BPA，因此这些发现对人类生殖健康具有严重的影响。该应用中概述的研究将使用小鼠模型来测试胎儿BPA暴露对女性生殖寿命的影响，并检查BPA对卵子早期阶段施加影响的机制。此外，我们将通过直接研究人类胎儿卵母细胞来将我们的发现从小鼠转化为人类，以确定BPA是否会类似地影响人类的早期卵子发生。最后，我们将测试遗传变异对生物活性BPA到达特定组织以及组织对BPA的组织反应的能力的影响。这些研究的合并数据将增强我们对这种化学物质造成的人类生育风险的理解。