Prenatal endocrine-disrupting chemicals and social/cognitive risk in mothers and infants: Potential biologic pathways

母婴互动为婴儿的社会/认知发展奠定了行为基础和轨迹。 父母的社会行为特别容易受到内分泌干扰化学品的影响，因为这些行为 是由荷尔蒙启动和社会/父母大脑的组织形成的。众所周知，在子宫内， 双酚A（BPA）暴露会扰乱动物和人类的神经行为发育。的途径 将子宫内BPA暴露与神经行为发育联系起来可能涉及子宫内的直接影响和间接影响。 通过破坏产后母婴互动产生的影响。迄今为止，很少有人类研究将产前 BPA暴露于改变母婴相互作用或检查这种影响的后果， 神经行为发育大多数人类文献都确定了BPA对年龄较大的儿童的影响。在啮齿类动物 和灵长类动物模型，产前暴露于双酚A破坏产妇护理和后代的社会行为， 表观遗传变化在人类中，这些对母婴互动的间接影响以及相关的 表观遗传机制尚未研究。因此，我们有可能低估BPA的全面影响。 暴露，我们目前还不知道BPA可能会破坏发育的途径。虽然 双酚A已从许多消费品中去除，它已被结构类似物双酚-s所取代。 (BPS)和双酚F（BPF），其可能具有类似的有害作用。本研究旨在将研究结果 从动物模型中询问人类产前BPA，BPS，BPF（BP）暴露增加是否预示着 最佳的产妇护理/母婴互动和婴儿/幼儿发展。此外，我们还问， 暴露与先前显示的母亲和婴儿基因中相应的表观遗传变化有关 受产前BPA暴露的影响：雌激素受体α（ESR 1：与母体 行为）和脑源性神经营养因子（BDNF;与婴儿神经可塑性和认知有关）。在 我们的翻译方法，我们招募怀孕期间的妇女，使用多种方法评估产前BP暴露， 在妊娠第三个三个月期间收集的尿液样本。我们评估母婴互动， 母亲和婴儿之间的每时每刻的相互影响的措施，提供了一个更微妙的 测量BP对人类的影响，我们评估了12岁时婴儿/幼儿的社会和认知发展， 24个月。在连续收集的口腔拭子中，我们评估了母亲中ESR 1的DNA甲基化， 婴儿和BDNF的婴儿，了解如何早期生活BP暴露改变这些途径。 了解BP对孕产妇保健和母婴互动的影响对于揭示 BP破坏神经发育的途径。该R 01解决了我们在 了解产前内分泌干扰化学品如何改变母婴互动，婴儿/幼儿 发展，以及相关的表观遗传过程，以及对预防和减轻 BP对神经发育的影响

Mother-infant interaction sets the behavioral foundation and trajectory for infant social/cognitive development. Parental social behaviors are especially vulnerable to endocrine-disrupting chemicals because these behaviors are shaped by hormonal priming and by the organization of the social/parental brain. It is known that in utero bisphenol A (BPA) exposure disturbs neurobehavioral development in animals and in humans. The pathways linking in utero BPA exposure to neurobehavioral development likely involve direct effects in utero, and indirect effects via disruption of postnatal mother-infant interactions. To date, little human study has linked prenatal BPA exposure to altered mother-infant interaction or examined the consequence of this effect on neurobehavioral development. Most of the human literature identifies effects of BPA in older children. In rodent and primate models, prenatal exposure to BPA disrupts maternal care and offspring social behavior via epigenetic changes. In humans, these indirect effects on mother-infant interaction and the associated epigenetic mechanisms have not been examined. We thus risk underestimating the full impact of BPA exposure, and we currently do not know the pathways through which BPA may disrupt development. Although BPA has been removed from many consumer products, it has been replaced by structural analogs, bisphenol-s (BPS) and bisphenol-f (BPF), which may have similar detrimental effects. This study aims to translate findings from animal models to ask whether increased prenatal BPA, BPS, BPF (BP) exposure in humans predicts less optimal maternal care/mother-infant interaction and infant/toddler development. Moreover we ask whether this exposure is associated with corresponding epigenetic changes in mother and infant in genes previously shown to be impacted by prenatal BPA exposure in rodents: estrogen receptor alpha (ESR1: implicated in maternal behavior) and brain-derived neurotrophic factor (BDNF; implicated in infant neural plasticity and cognition). In our translational approach, we recruit women during pregnancy, assess prenatal BP exposure using multiple urine samples collected during the 3rd trimester of pregnancy. We assess mother-infant interaction with measures of moment-by-moment reciprocal influences between mother and infant, providing a more nuanced measure of the effects of BP in humans, and we assess infant/toddler social and cognitive development at 12 and 24 months. In serially collected buccal swabs, we assess DNA methylation of ESR1 in the mother and infant and of BDNF in the infant to understand how early life BP exposure alters these pathways. Understanding the effects of BP on maternal care and mother-infant interaction is essential to revealing the pathways through which BP acts to disrupt neurodevelopment. This R01 addresses a critical gap in our understanding of how prenatal endocrine-disrupting chemicals alter mother-infant interaction, infant/toddler development, and associated epigenetic processes, with implications for strategies to prevent and mitigate the impact of BP on neurodevelopment.