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

E3Gen：接触毒物对生命过程、健康和神经认知的多代影响 元素出生队列中的结局 摘要 敏感发育阶段环境毒物对健康和疾病风险的影响 月经已被认识了近20年，成年人的发育起源突出了这一点 疾病假说和生命过程流行病学。然而，了解新机制的潜力 这些框架中隐含的信息尚未完全实现。很少有环保团体效仿 超过青春期的母子二元，排除了理解疾病长期影响的能力 青壮年和围绝经期的毒物暴露--这两个动态生命阶段的特征是 增加代谢综合征的风险和神经认知过程的潜在变化。E3Gen 项目，基于我们与国家研究所长达22年的非常成功的研究合作 Salud Pública de墨西哥(INSP)包括三个出生队列的妇女，最初是从1994年招募的- 2004年，他们的孩子现在12-22岁，下一代孙子现在是 出生了。此R24应用程序利用了我们正在进行的早期研究的研究基础架构 墨西哥暴露于环境毒物(元素)队列和由NIEHS资助的三个 密歇根大学的研究中心，创造了一个无与伦比的机会，推出了新的研究 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和 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 E3Gen多代队列的科学完整性和实施战略，以鼓励 850名38~50岁母亲及其子女参与和预防失访的调查 12-22岁，同时还招募了90名孙子孙女，预计在未来5年内出生 几年；2)考虑到表观遗传学、口腔健康和口腔的作用，为未来的科学研究做准备 微生物组在内分泌干扰物和金属对代谢影响中的作用 以及三代元素参与者的神经认知结果； 开发和测试 新的数据管理技术可改进和丰富数据集成和协调、数据 共享，以及跨项目的数据交流。

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.