Endocrine Disruptors: Maternal Estrogen, Metabolism and Fetal Fatty Acid Supply

内分泌干​​扰物：母体雌激素、代谢和胎儿脂肪酸供应

• 批准号: 9115600
• 负责人: Rita S. Strakovsky
• 金额: $ 9.92万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9115600
• 关键词: Address; Adipose tissue; Affect; Age; Animal Experimentation; Animal Model; Animals; Biometry; Birth; Body fat; Cell model; Chemicals; Child; Data; Development; Development Plans; Endocrine; Endocrine Disruptors; Enrollment; Environmental Epidemiology; Environmental Health; Epidemiologic Studies; Epidemiology; Estrogen Metabolism; Estrogens; Excretory function; Exposure to; Fatty Acids; Fatty acid glycerol esters; Fetal Development; Fetus; Goals; Gonadal Steroid Hormones; Health; Hip region structure; Human; Illinois; Individual; Infant; Knowledge; Life; Maternal Exposure; Maternal Health; Maternal Physiology; Measures; Mediating; Mentors; Mothers; National Institute of Environmental Health Sciences; Nutrient; Obesity; Omega-3 Fatty Acids; Outcome; Overweight; Perinatal Exposure; Phase; Physiological Adaptation; Physiological Processes; Polyunsaturated Fatty Acids; Population; Pregnancy; Process; Public Health; Research; Rodent; Role; Sampling; Second Pregnancy Trimester; Thigh structure; Third Pregnancy Trimester; Time; Toxic Environmental Substances; Toxicology; Training; Umbilical Cord Blood; Universities; Urine; Waist-Hip Ratio; Weight; Woman; Work; base; bisphenol A; career; career development; cognitive development; cohort; environmental chemical; estrogen disruption; experience; fetal; implantation; nervous system development; neurodevelopment; novel; phthalates; prenatal; reproductive; sex; urinary

 DESCRIPTION (provided by applicant): This K99/R00 will prepare Dr. Rita Strakovsky for an independent research career. Dr. Strakovsky has extensive training using animal models to address questions related to maternal health, but has a strong desire to expand her training to epidemiology. An exceptional team of mentors has been assembled with expertise in epidemiology, biostatistics, environmental health, and reproductive/endocrine toxicology. Two mentors have extensive experience integrating animal and human research. The primary training goal is to develop expertise in environmental epidemiology, with the eventual goal of applying knowledge from mechanistic lab animal research when formulating epidemiologic research questions. The career development plan includes rigorous course work in epidemiology/biostatistics as well as mentored research in environmental epidemiology. Women of reproductive age are exposed to bisphenol A (BPA) and phthalates on a daily basis. These chemicals can disrupt estrogen synthesis in animal models, but no human studies have assessed the relationship between BPA or phthalates and estrogen during pregnancy. Furthermore, no studies have assessed whether maternal adiposity can modify this relationship. In the mentored phase, Dr. Strakovsky will leverage an ongoing pregnancy cohort to investigate the association between these chemicals and maternal estrogen levels, and whether maternal % body fat or waist/hip ratio can modify this relationship (Aim 1). BPA and phthalates will be assessed in pooled urine from 5 samples collected across pregnancy. Estrogens will be measured in 3 urine samples collected at the low, middle, and peak concentrations of gestational estrogen. It is hypothesized that women with higher urinary BPA or phthalate metabolites across pregnancy will have lower urinary estrogen metabolites throughout pregnancy, and maternal % body fat and waist/hip ratio and/or the infant's sex will modify this relationship. Factors that affect estrogen levels in the mother could alter the accretion and release of maternal adipose tissue stores, and thus fetal LC-PUFA supply, which is critical for neurodevelopment. Studies in rodents show that BPA and phthalates can alter placental LC-PUFA content (which is directly related to fetal LC-PUFA supply), but it is not known whether this also occurs in humans. In the independent phase, Dr. Strakovsky will investigate the relationship between maternal BPA and phthalate exposures and fetal LC-PUFA supply (Aim 2). Cord blood collected at birth will be used to measure arachidonic, linoleic, α-linolenic, docosahexaenoic, and the n-6/n-3 fatty acid ratio. It is hypothesized that higher urinary BPA or phthalate metabolites across pregnancy will be associated with increased n-6/n-3 ratio, and decreased cord blood LC-PUFAs. It is further hypothesized that the association of BPA or phthalates with maternal estrogen will mediate this relationship, and that the relationship will be modified by the infant's sex. These findings will provide novel information regarding the impact of two widespread environmental toxicants on maternal and fetal health.

 描述（由申请人提供）：本 K99/R00 将为丽塔·斯特拉科夫斯基 (Rita Strakovsky) 博士的独立研究生涯做好准备。斯特拉科夫斯基 (Strakovsky) 博士接受过使用动物模型解决与孕产妇健康相关问题的广泛培训，但强烈希望将她的培训扩展到以下领域。流行病学。由流行病学、生物统计学、环境健康和生殖/内分泌毒理学方面的专业知识组成的优秀导师团队拥有丰富的动物和人类研究经验。目标是发展环境流行病学方面的专业知识，最终目标是在制定流行病学研究问题时应用机械实验动物研究的知识。职业发展计划包括严格的流行病学/生物统计学课程以及环境流行病学的指导研究。育龄儿童每天都会接触双酚 A (BPA) 和邻苯二甲酸盐，这些化学物质会扰乱动物模型中的雌激素合成，但尚无人体研究评估 BPA 或邻苯二甲酸盐之间的关系。此外，没有研究评估母亲肥胖是否会改变这种关系。在指导阶段，斯特拉科夫斯基博士将利用正在进行的怀孕队列来研究这些化学物质与母亲雌激素水平之间的关系，以及母亲的身体百分比是否会改变。脂肪或腰臀比可以改变这种关系（目标 1），将在怀孕期间收集的 5 个样本的合并尿液中评估雌激素，并在低浓度、中浓度和峰值浓度下测量雌激素。据了解，怀孕期间尿中 BPA 或邻苯二甲酸盐代谢物较高的女性在整个怀孕期间尿中雌激素代谢物较低，而母亲的身体脂肪百分比和腰臀比和/或婴儿的性别会改变这种关系。母亲体内的雌激素水平可能会改变母体脂肪组织储存的积累和释放，从而改变胎儿的 LC-PUFA 供应，这对啮齿类动物的神经发育至关重要。邻苯二甲酸盐可以改变胎盘的 LC-PUFA 含量（这与胎儿的 LC-PUFA 供应直接相关），但尚不清楚这是否也会发生在人类身上。在独立阶段，Strakovsky 博士将研究母体 BPA 和邻苯二甲酸盐之间的关系。暴露和胎儿 LC-PUFA 供应（目标 2） 出生时收集的脐带血将用于测量花生四烯酸、亚油酸、α-亚麻酸、二十二碳六烯酸、 n-6/n-3 脂肪酸比率据推测，怀孕期间较高的尿 BPA 或邻苯二甲酸酯代谢物与 n-6/n-3 比率增加以及脐带血 LC-PUFA 减少有关。证实 BPA 或邻苯二甲酸盐与母体雌激素的关联将调节这种关系，并且这种关系将 这些发现将提供有关两种广泛的环境毒物对孕产妇和胎儿健康影响的新信息。