Exposure to phthalate mixtures in pregnancy and long-term consequences for maternal metabolic and hormonal status

怀孕期间接触邻苯二甲酸盐混合物以及对母亲代谢和荷尔蒙状态的长期影响

• 批准号: 10231234
• 负责人: Rita S. Strakovsky
• 金额: $ 41.58万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10231234
• 关键词: Affect; Age; Alzheimer' s Disease; Anabolism; Behavior; Birth; Blood Pressure; Blood Vessels; Characteristics; Child; Cohort Studies; Complex; Complex Mixtures; Desire for food; Development; Elderly; Endocrine; Endocrine Disruptors; Endocrine disruption; Endothelium; Energy Metabolism; Enrollment; Estradiol; Estriol; Estrogens; Estrone; Exposure to; Fetal Development; First Births; Food; Gestational Diabetes; Glucose; Glycosylated hemoglobin A; Health; Hormonal; Illinois; Individual; Insulin; Life; Malignant Neoplasms; Maternal Exposure; Maternal Health; Mediating; Mental Depression; Metabolic; Metabolic Diseases; Metabolic dysfunction; Metabolism; Mothers; Non-Insulin-Dependent Diabetes Mellitus; Nonesterified Fatty Acids; Nutrient; Obesity; Ovary; Personal Satisfaction; Play; Pregnancy; Pregnancy Outcome; Pregnant Women; Public Health; Research; Rest; Risk; Role; Source; Testing; Vascular Cell Adhesion Molecule-1; Vascular Endothelial Growth Factors; Weight; Woman; Women' s Health; Work; blood glucose regulation; cardiovascular disorder risk; child bearing; cohort; estrogen disruption; experience; fasting glucose; fetal; gestational weight gain; implantation; improved; insight; insulin sensitivity; intercellular cell adhesion molecule; maternal obesity; maternal weight; middle age; novel; obesity risk; parity; personal care products; phthalates; postnatal; prenatal; prevent; prospective; public health intervention; virtual

PROJECT SUMMARY As many as 86% of women will give birth to at least one child, and pregnancy has long-term consequences for women’s metabolic health, including obesity and glucose homeostasis. However, little is understood about modifiable factors in pregnancy that can improve women’s health postnatally. Phthalates are endocrine disrupting chemicals to which almost all women are exposed from personal care products and food contact materials. Recent evidence suggests that phthalate exposure in pregnancy is associated with disrupted gestational weight gain and glucose homeostasis in mothers. However, whether these metabolic disruptions persist postnatally is not currently known. Therefore, we will leverage an ongoing pregnancy cohort study that has already assessed phthalate concentrations in pregnant women to follow these mothers and ask whether prenatal phthalate exposure is associated with disrupted adiposity and metabolism 4-7 years later. Importantly, we will assess cumulative exposure to a complex mixture of phthalates, since pregnant women have concurrent exposure to numerous phthalates. Phthalates can disrupt estrogen biosynthesis, and several studies (including our preliminary work) suggest that phthalate exposures are associated with disrupted estrogen levels in pregnant women. This is concerning in pregnancy because estrogens have numerous critical functions in pregnant women, including implantation, fetal nutrient transport, and parturition. While estrogenic disruption by phthalates in pregnancy could have deleterious consequences for fetal development and pregnancy outcomes, whether these hormonal disruptions persist postnatally to impact maternal health is not known. Estrogen disruption that persists after pregnancy is potentially harmful for women’s life-long health because in non-pregnant women, estrogens regulate maternal metabolic health, including weight, metabolic efficiency, insulin sensitivity, and appetite. Therefore, the current study will also assess whether exposure to a complex mixture of phthalates in pregnancy is associated with disrupted estrogen levels in women postnatally, and whether these prenatal endocrine disruptions that persists postnatally drive maternal metabolic dysregulations.

项目概要 多达 86% 的女性将至少生育一个孩子，怀孕会对女性产生长期影响 然而，人们对女性的代谢健康知之甚少，包括肥胖和葡萄糖稳态。 怀孕期间可以改善女性产后健康的可改变因素是内分泌。 破坏几乎所有女性都因个人护理产品和食品接触而接触到的化学物质 最近的证据表明，怀孕期间接触邻苯二甲酸盐与破坏有关。 然而，妊娠期体重增加和母亲的葡萄糖稳态是否会受到干扰。 目前尚不清楚产后是否持续存在，因此，我们将利用一项正在进行的妊娠队列研究。 已经评估了孕妇的邻苯二甲酸盐浓度，以跟踪这些母亲并询问是否 产前接触邻苯二甲酸盐与 4-7 年后肥胖和新陈代谢紊乱有关。 我们将评估对邻苯二甲酸盐复杂混合物的累积暴露，因为孕妇同时患有 接触大量邻苯二甲酸盐。 邻苯二甲酸盐会破坏雌激素的生物合成，多项研究（包括我们的初步工作）表明 邻苯二甲酸盐暴露与孕妇雌激素水平紊乱有关，这对于孕妇来说是令人担忧的。 怀孕，因为雌激素对孕妇有许多关键功能，包括着床、胎儿 而怀孕期间邻苯二甲酸盐破坏雌激素可能有害。 对胎儿发育和妊娠结局的影响，这些荷尔蒙干扰是否持续存在 产后是否会影响孕产妇健康尚不清楚，怀孕后雌激素干扰是否可能持续存在。 对女性的终生健康有害，因为在非怀孕女性中，雌激素调节母体代谢 健康状况，包括体重、代谢效率、胰岛素敏感性和食欲。因此，目前的研究将。 还评估在怀孕期间接触邻苯二甲酸盐的复杂混合物是否与破坏有关 女性产后的雌激素水平，以及这些产前内分泌紊乱是否会在产后持续存在 导致母体代谢失调。