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

项目总结 多达86%的女性将至少生一个孩子，怀孕对 女性的代谢健康，包括肥胖和血糖动态平衡。然而，人们对此知之甚少。 孕期可改变的因素，可改善妇女出生后的健康。邻苯二甲酸酯是内分泌的 扰乱几乎所有女性从个人护理产品和食物接触中接触到的化学物质 材料。最近的证据表明，怀孕期间接触邻苯二甲酸盐与精神紊乱有关 孕期体重增加与母亲血糖动态平衡。然而，这些代谢紊乱是否 目前尚不清楚是否会在出生后持续存在。因此，我们将利用一项正在进行的怀孕队列研究 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 出生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。重要的是 我们将评估与邻苯二甲酸盐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。 邻苯二甲酸盐可以扰乱雌激素的生物合成，一些研究(包括我们的初步工作)表明 孕妇接触邻苯二甲酸盐与雌激素水平紊乱有关。这是关于在 怀孕是因为雌激素对孕妇有许多关键功能，包括着床、胎儿 营养物质的运输和分娩。而怀孕期间邻苯二甲酸盐对雌激素的干扰可能是有害的 对胎儿发育和妊娠结局的影响，无论这些荷尔蒙紊乱是否持续 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有可能 对妇女的终身健康有害，因为在非怀孕妇女中，雌激素调节母亲的代谢 健康，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 还要评估怀孕期间接触复杂的邻苯二甲酸盐混合物是否与精神紊乱有关 女性出生后的雌激素水平，以及这些产前内分泌紊乱是否会在出生后持续 导致母体代谢紊乱。

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.