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

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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 Although BPA has been removed from many consumer products, it has been replaced by structural analogs, bisphenol-s (BPS) and bisphenol-f (BPF), which may have similar detrimental effects.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.