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

项目摘要 多达86%的女性至少会生一个孩子，而怀孕会对女性产生长期影响。 女性的代谢健康，包括肥胖和葡萄糖稳态。然而，人们对 怀孕期间可以改变的因素，可以改善妇女的健康产后。邻苯二甲酸盐是内分泌的 破坏几乎所有女性都从个人护理产品和食物接触中暴露的化学物质 材料.最近的证据表明，妊娠期邻苯二甲酸酯暴露与破坏 妊娠期体重增加和母亲体内葡萄糖稳态。然而，这些代谢紊乱是否 目前尚不清楚产后是否持续存在。因此，我们将利用正在进行的妊娠队列研究， 已经评估了孕妇体内的邻苯二甲酸酯浓度，以跟踪这些母亲，并询问是否 产前邻苯二甲酸酯暴露与4-7年后肥胖和代谢紊乱有关。重要的是， 我们将评估邻苯二甲酸酯复杂混合物的累积暴露，因为孕妇同时 接触大量邻苯二甲酸盐 邻苯二甲酸盐可以破坏雌激素的生物合成，一些研究（包括我们的初步工作）表明， 邻苯二甲酸酯暴露与孕妇雌激素水平紊乱有关。这是关于在 怀孕，因为雌激素在孕妇中具有许多关键功能，包括着床、胎儿发育、妊娠和妊娠。 营养运输和分娩。虽然邻苯二甲酸酯在怀孕期间对雌激素的破坏可能会对 对胎儿发育和妊娠结局的影响，这些激素干扰是否持续 产后对产妇健康的影响尚不清楚。怀孕后持续的雌激素紊乱可能是 对妇女的终身健康有害，因为在非怀孕妇女中，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，本研究将 还评估了妊娠期接触复杂的邻苯二甲酸酯混合物是否与破坏 雌激素水平的妇女产后，以及这些产前内分泌干扰是否持续产后 导致母体代谢失调

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.