Environmental bisphenol exposure, infant brain and behavior: Human and animal models

子宫内双酚A（BPA）暴露会干扰动物和人类的神经行为发育。的 将子宫内BPA暴露与神经行为发育联系起来的途径可能涉及子宫内对神经行为发育的直接影响。 婴儿大脑发育，以及通过破坏产后母婴互动产生的间接影响。父母 社会行为可能特别容易受到内分泌干扰化学品的影响，如BPA， 行为是由荷尔蒙启动和社会/父母大脑的组织形成的。大部分 人类文献确定了BPA对年龄较大的儿童的影响，很少关注生命的第一年。在啮齿动物和 在灵长类动物模型中，子宫内暴露于BPA会破坏后代的认知和社会发育以及母体护理 通过表观遗传变化。在人类中，BPA对婴儿大脑发育和注意力的直接影响， BP诱导的母婴相互作用变化对这些效应的调节尚未得到研究。我们 因此，他们不知道BPA可能破坏发育的途径。虽然BPA已被删除 从许多消费品中，它已被结构类似物双酚-s（BPS）和双酚-f所取代。 (BPF)，这可能具有类似的有害影响。这项研究将：1）检查子宫内血压之间的关联 （联合暴露）暴露和婴儿大脑功能和注意力，2）进行平行的啮齿动物研究， 子宫内BP暴露对大脑细胞和分子变化的影响，以及3）将人类方法 研究母婴相互作用，用于我们的啮齿动物模型，并确定BP对这些 相互影响。在人类和啮齿类动物中，我们询问是否检测到子宫内血压 脑和认知发育受BP引起的母婴互动变化的调节。在我们 翻译的方法，我们招募了1个月和9个月大的婴儿，并评估婴儿的大脑功能和注意力 在两个时间点，我们利用先前资助的母婴互动测量来测试其 对这些关联的调节作用。在我们的平行啮齿动物模型中，我们测量了BP暴露对 子代大脑皮层基因表达、结构、注意力和母婴互动质量。 影响：本R 01解决了我们对子宫内暴露于内分泌干扰物的理解中的一个关键空白。 化学物质会改变婴儿的大脑和认知功能。了解这些影响对于开发 筛选工具和干预对神经发育的下游影响。R 01还提供 初步数据，用于该团队之间未来的翻译合作。未来的动物研究将 通过交叉培养实验来解开BP的直接和间接影响，人类研究将 跟踪这一队列到学龄，以研究BP诱导的神经发育影响的神经相关性。

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 on infant brain development, and indirect effects via disruption of postnatal mother-infant interactions. Parental social behaviors may be especially vulnerable to endocrine-disrupting chemicals such as BPA as these behaviors are shaped by hormonal priming and by the organization of the social/parental brain. Most of the human literature identifies effects of BPA in older children, with little focus on the first year of life. In rodent and primate models, in utero exposure to BPA disrupts offspring cognitive and social development and maternal care via epigenetic changes. In humans, the direct effect of BPA on infant brain development and attention, and the modulation of these effects by BP-induced changes to mother-infant interaction, have not been examined. We thus 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 Although BPA has been removed from many consumer products, it has been replaced by structural analogs, bisphenol-s (BPS) and bisphenol-f (BPF), which may have similar detrimental effects.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 will: 1) examine associations between in utero BP (combined exposure) exposure and infant brain function and attention, 2) conduct a parallel rodent study of the effects of in utero BP exposure on cellular and molecular changes in the brain, and 3) translate a human method of studying mother-infant interaction for use in our rodent model and determine the effects of BP on these caregiving interactions. In both humans and rodents, we ask whether associations detected between in utero BP and brain and cognitive development are moderated by BP-induced change in mother-infant interaction. In our translational approach, we recruit infants at 1- and 9-months old and assess infant brain function and attention at two timepoints, and we leverage previously funded measurement of mother-infant interaction to test its moderating effects on these associations. In our parallel rodent model, we measure effects of BP exposure on offspring cortical gene expression, structure, attention and quality of mother-infant interactions. Impact: This R01 addresses a critical gap in our understanding of how in utero exposure to endocrine-disrupting chemicals alters infant brain and cognitive function. Understanding these effects is essential to developing screening tools and intervention for downstream effects on neurodevelopment. The R01 also provides preliminary data for use in future translational collaborations among this team. Future animal studies will disentangle the direct and indirect effects of BP through cross-fostering experiments, and human studies will follow this cohort into school age to investigate neural correlates of BP-induced effects on neurodevelopment.