Developmental consequences of prenatal exposure to endocrine disruptor chemicals - An investigation of epigenetic mechanisms in the Duisburg Birth Cohort Study

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The investigation of effects of environmental contaminants on human health is a major public health issue. Exposure to environmental toxins especially during sensitive periods of pre- and early postnatal development may result in long-lasting alterations of brain structure and function and increase the risk of mental health problems in adolescence. Although exposure of the general population has decreased over the last decades, especially prenatal exposure toendocrine disrupting chemicals (EDCs) is still of concern because of the increased vulnerability of the immature organism. The goal of this study is to investigate psychosocial development and DNA methylation levels in a well-characterized birth cohort study of children for whom objective measures of the internal exposure to chemicals as well as psychological and anthropometric measures are available at multiple time-points. We aim to test whether EDC exposure leads to long-term consequences in cognitive and psychosocial functioning, pubertal developmental and sex-typical behaviour in early adolescence. Furthermore, we aim to investigate whether prenatal exposure to EDCs leads to epigenetic modifications in genes coding for gonadal steroid hormone receptors (and their targets) involved in the orchestration of brain development and known to be affected by endocrine disruptors. We also aim to explore exposure-associated changes in DNA methylation more globally by examining genome-wide DNA methylation patterns. Furthermore, we will test whether the effects of EDC exposure on outcomes are mediated via epigenetic modifications. The prospective-longitudinal nature of the study, which includes objective measures of the internal exposure to chemicals represents a unique opportunity to come to a better understanding of the long-term developmental outcomes and associated mechanisms of EDC exposure.