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: 8133816
• 负责人: Patricia Hunt
• 金额: $ 51.44万
• 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/8133816
• 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. PUBLIC HEALTH RELEVANCE: These studies will assess the effects on human reproductive health of bisphenol A (BPA), a member of a class of chemicals known as endocrine disrupting chemicals. Specifically, the studies outlined in this application focus on BPA-induced effects on gametogenesis in female mice and - for the first time - directly address the possibility that BPA exposure affects gamete production in humans as well.

描述（由申请人提供）：非整倍性，即染色体的丢失或获得，是人类妊娠失败和出生缺陷的主要原因。大多数非整倍体是由母体不分离引起的，但其病因仍不清楚。长期以来，人们一直怀疑环境因素发挥了作用，但直到最近，这一点还没有得到直接证据的证实。我们实验室最近的研究表明，怀孕期间接触雌激素化学物质双酚 A (BPA) 会显着增加小鼠卵子和胚胎染色体异常的频率。由于人类每天都会接触 BPA，这些发现对人类生殖健康具有严重影响。本申请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，并研究 BPA 对卵子发生早期阶段发挥作用的机制。此外，我们将通过直接研究人类胎儿卵母细胞，将我们的研究结果从小鼠转化为人类，以确定 BPA 是否同样影响人类早期卵子发生。最后，我们将测试遗传变异对生物活性 BPA 到达特定组织的能力以及组织对 BPA 反应的影响。这些研究的综合数据将增强我们对这种化学品对人类生育能力造成的风险的了解。 公共健康相关性：这些研究将评估双酚 A (BPA) 对人类生殖健康的影响，双酚 A 是一类被称为内分泌干扰物的化学物质的成员。具体来说，本申请中概述的研究重点关注 BPA 对雌性小鼠配子发生的影响，并首次直接解决了 BPA 暴露也会影响人类配子产生的可能性。