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发展轨迹。 父母的社交行为特别容易受到内分泌干扰化学物质的影响，因为这些行为 是由荷尔蒙启动和社会/父母大脑的组织塑造的。众所周知，在子宫内 双酚A(BPA)暴露会干扰动物和人类的神经行为发育。小路 在子宫内将双酚A暴露与神经行为发育联系起来可能涉及在子宫内的直接影响，以及间接影响 产后母婴互动中断所产生的影响。到目前为止，很少有人类研究将产前与 双酚A暴露在母婴相互作用改变中，或检查这种影响的后果 神经行为发育。大多数人类文献都指出了双酚A对年龄较大的儿童的影响。在啮齿动物中 和灵长类动物模型，产前暴露于双酚A通过以下方式扰乱母体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 表观遗传机制尚未得到检验。因此，我们有可能低估双酚A的全部影响。 我们目前还不知道双酚A可能通过什么途径扰乱发育。虽然 双酚A已从许多消费品中移除，取而代之的是结构类似物，双酚-S 和双酚-f(BPF)，它们可能具有类似的有害影响。这项研究旨在将研究结果转化为 从动物模型来问，产前暴露于人类的BPA、BPS、BPF(BP)增加是否预测更少 最佳产妇护理/母婴互动和婴幼儿发展。此外，我们问这是不是 暴露与母亲和婴儿在先前显示的基因中相应的表观遗传变化有关 受孕期双酚A暴露对啮齿动物的影响：雌激素受体α(ESR1：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……里面 我们的翻译方法是，我们招募怀孕期间的女性，使用多个 在妊娠晚期采集尿液样本。我们用以下方法评估母婴互动 衡量母婴之间每时每刻的相互影响，提供更细微的 测量血压对人类的影响，并在12岁时评估婴儿/幼儿的社交和认知发展 还有24个月。在连续收集的口腔拭子中，我们评估了母亲和母亲中ESR1的DNA甲基化 婴儿和婴儿脑源性神经营养因子的变化，以了解早期血压暴露如何改变这些途径。 了解BP对产妇护理和母婴互动的影响对于揭示 BP扰乱神经发育的途径。此R01解决了我们的 了解产前内分泌干扰物如何改变母婴、婴儿/幼儿的相互作用 发展和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 Although BPA has been removed from many consumer products, it has been replaced by structural analogs, bisphenol-s (BPS) and bisphenol-f (BPF), which may have similar detrimental effects.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.