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

环境污染物对人体健康影响的研究是一个重大的公共卫生问题。暴露于环境毒素，特别是在产前和产后早期发育的敏感时期，可能导致大脑结构和功能的长期改变，并增加青春期心理健康问题的风险。尽管在过去的几十年里，一般人群的暴露量有所减少，但由于未成熟生物体的脆弱性增加，特别是产前暴露于内分泌干扰物（EDCs）仍然令人担忧。本研究的目的是调查心理社会发展和DNA甲基化水平在一个良好的特征化的出生队列研究的儿童的内部暴露于化学品的客观措施，以及心理和人体测量的措施，可在多个时间点。我们的目的是测试EDC暴露是否会导致认知和心理社会功能，青春期发育和青春期早期性典型行为的长期后果。此外，我们的目标是调查产前暴露于内分泌干扰物是否会导致编码性腺类固醇激素受体（及其靶点）的基因发生表观遗传修饰，这些受体参与大脑发育的协调，并且已知会受到内分泌干扰物的影响。我们还旨在通过检查全基因组DNA甲基化模式，更全面地探索与DNA甲基化相关的变化。此外，我们将测试EDC暴露对结局的影响是否通过表观遗传修饰介导。该研究的前瞻性纵向性质包括对化学品内部暴露的客观测量，这是一个独特的机会，可以更好地了解EDC暴露的长期发育结局和相关机制。

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.