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

产前接触内分泌干扰物化学物质的发育后果 - 杜伊斯堡出生队列研究中表观遗传机制的调查

• 批准号: 353803853
• 负责人: Professor Dr. Robert Kumsta
• 金额: --
• 依托单位: Horst-Görtz-Institut für IT-Sicherheit (HGI)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/353803853?language=en
• 关键词: Developmental; consequences; prenatal; exposure; endocrine

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.

调查环境污染物对人类健康的影响是一个重大的公共卫生问题。接触环境毒素，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，并增加青少年出现精神健康问题的风险。尽管在过去的几十年里，普通人群的暴露已经减少，特别是产前暴露于内分泌干扰化学物质（EDCs）仍然令人担忧，因为未成熟生物体的脆弱性增加。本研究的目的是在一项特征明确的出生队列研究中调查儿童的心理社会发展和DNA甲基化水平，这些儿童在多个时间点对化学物质的内部暴露进行客观测量，以及心理和人体测量测量。我们的目的是测试EDC暴露是否会导致认知和社会心理功能，青春期发育和青春期早期的性典型行为的长期后果。此外，我们的目的是研究产前暴露于EDCs是否会导致编码性腺类固醇激素受体（及其靶标）的基因的表观遗传修饰，这些基因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，更全面地探索暴露相关的DNA甲基化变化。此外，我们将测试EDC暴露对结果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，包括对化学物质内部暴露的客观测量，为更好地了解EDC暴露的长期发展结果和相关机制提供了独特的机会。