E3Gen: Multigenerational Effects of Toxicant Exposures on Life Course Health and Neurocognitive Outcomes in the ELEMENT Birth Cohorts

E3 Gen：毒物暴露对生命过程健康和神经认知的多代影响 ELEMENT出生队列的结局 总结 环境毒物对敏感发育期健康和疾病风险的影响 近20年来，人们已经认识到，正如成年人的发育起源所强调的那样， 疾病假说和生命过程流行病学。然而，理解新机制的潜力 这些框架所隐含的目标尚未充分实现。很少有环境群体追随 青春期后的母子二人组，排除了理解长期影响的能力， 青年期和围绝经期的毒物暴露-这两个动态生命阶段的特征是 代谢综合征的风险增加和神经认知过程的潜在变化。E3Gen 项目，基于我们非常成功的，22年的研究合作与国家研究所 墨西哥公共卫生协会（INSP）由三个出生队列的妇女组成，最初是从1994年开始招募的， 2004年，他们的孩子现在12-22岁，下一代的孙子目前正在 出生这个R24应用程序利用了我们正在进行的早期生命研究的研究基础设施 墨西哥环境毒物（ELEMENT）队列和三个NIEHS资助的 中心在密歇根大学，创造了一个无与伦比的机会，推出新的研究， 最大限度地利用现有的生物储存库和丰富的重复毒物暴露数据库， 代谢和神经认知结果，并促进加速数据和资源共享， 更大的环境健康科学界。具体目标是：1）保持和提高 E3 Gen多代群体的科学完整性，并实施鼓励 对850名年龄在38-50岁之间的母亲、其年龄在18 - 19岁之间的子女、 12-22岁，同时目前还招募了90个孙子，预计将在未来五年内出生 2）为未来的科学研究做准备，考虑表观遗传学，口腔健康和口腔疾病的作用 微生物组在介导内分泌干扰化学品（EDCs）和金属对代谢的影响方面的作用 三代ELEMENT参与者的神经认知结果; 3） 开发和测试 新的数据管理技术，以改善和丰富数据集成和协调，数据 共享和跨项目数据通信。

E3Gen: Multigenerational effects of toxicant exposures on life course health and neurocognitive outcomes in the ELEMENT birth cohorts SUMMARY The impact of environmental toxicants on health and disease risk during sensitive developmental periods has been recognized for nearly 20 years, as highlighted by the developmental origins of adult disease hypothesis and life course epidemiology. Yet, the potential to understand novel mechanisms implicit in these frameworks has not been fully realized. Few environmental cohorts have followed mother-child dyads beyond adolescence, precluding the ability to understand long-term impacts of toxicant exposures in young adulthood and perimenopause—both dynamic life stages characterized by increased risk of metabolic syndrome and potential changes in neurocognitive processes. The E3Gen project, based on our highly successful, 22-year research collaboration with the Instituto Nacional de Salud Pública de Mexico (INSP), comprises three birth cohorts of women originally recruited from 1994- 2004, their children now aged 12-22 years, and the next generation of grandchildren currently being born. This R24 application leverages the research infrastructure of our ongoing studies in the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) cohorts and of three NIEHS-funded centers at the University of Michigan, creating an unparalleled opportunity launch new research that maximizes use of the existing biorepository and rich database of repeated toxicant exposures and metabolic and neurocognitive outcomes and that promotes accelerated data and resource sharing with the larger environmental health sciences community. Specific Aims are to: 1) Maintain and enhance the scientific integrity of the E3Gen multigenerational cohort and implement strategies to encourage participation and prevent loss to follow up among 850 mothers aged 38-50 years, their children aged 12-22 years, while also recruiting 90 grandchildren currently and projected to be born over the next five years; 2) Prepare for future scientific studies considering the roles of epigenetics, oral health and oral microbiome in mediating the impact of endocrine disrupting chemicals (EDCs) and metals on metabolic and neurocognitive outcomes across three generations of ELEMENT participants; 3) Develop and test novel data management techniques to improve and enrich data integration and harmonization, data sharing, and cross-project data communication.