环境内分泌干扰物母婴暴露对儿童肥胖的影响及其分子机制

Childhood obesity, with increasing prevalence, is a major scientific problem in the areas of medicine and public health all over the world in the 21st century, needing to be solved urgently. Childhood obesity is a complex disease involving environmental chemical pollution, genetic variation and abnormal epigenetic modification. However, its pathogenesis is still unknown and effective preventions and controls cannot be provided. This project will start with large birth cohort and animal models and apply methods in analytical chemistry, genomics, proteomics, epigenetics, metabolomics and bioinformatics, based on the evaluations of the epidemiological investigation and reproductive functions, , in order to determine the associations between EDCs exposure and childhood obesity, find the mechanism of candidate EDCs causing childhood obesity, identify the new biomarkers of exposure, effect and susceptibility of childhood obesity, and build up models for risk assessment of EDCs exposure causing childhood obesity . This project will provide a basis for early prevention, diagnosis and treatment of childhood obesity, and make contributions to improve the quality of the population and children's health.

儿童肥胖呈日益增加和流行趋势，是21世纪全球医学和公共卫生领域亟待研究和解决的重大科学问题。儿童肥胖与环境化学污染物、遗传因子改变、表观遗传修饰异常等密切相关，但其发病机制尚不清楚，更缺乏有效的综合防治措施。本项目拟以大样本出生队列和动物模型研究为切入点，以流行病学调查及生殖发育功能评价为基础，应用分析化学、基因组学、蛋白组学、表观遗传学、代谢组学、生物信息学等研究手段，明确环境内分泌干扰物（EDCs）暴露与儿童肥胖的相关性，阐明目标EDCs致儿童肥胖的分子机制，发现儿童肥胖新的接触、效应和易感生物标志，构建EDCs暴露致儿童肥胖的风险评估模型。为儿童肥胖的早期预防、诊断和治疗提供理论依据，为提高人口质量、促进儿童健康做出贡献。

儿童超重和肥胖已成为21世纪人类所面临的最严峻的公共卫生挑战之一。本项目旨在通过大样本病例-对照和出生队列研究，明确目标EDCs 暴露与儿童肥胖的相关性；并综合表观遗传学、转录组学、代谢组学等多组学信息，筛选并鉴定目标EDCs 作用的关键环节和靶点；通过构建目标EDCs暴露动物模型和体外试验，阐明该作用的相关分子机制，为预防和控制母婴目标EDCs 暴露提供直接依据。在项目实施阶段，课题组建立了较大规模的、以社区为中心的、囊括父母双方完整孕期信息与样本的南京医科大学出生队列并进行完善，构建了从妊娠期到学龄前期的生物样本库和数据资源库；建立了暴露组学和代谢组学平台，通过对目标EDCs 的危害识别、剂量-反应关系评定、暴露评定和危险度表征分析，构建了目标EDCs 暴露致儿童肥胖的风险评估/危险度评定模型，明确了代表性EDCs 暴露与儿童肥胖的相关性；采用ICR小鼠孕期染毒模型，阐明了孕期双酚A、邻苯二甲酸二(2-乙基)己酯和全氟辛酸等EDCs暴露对子代肥胖发生的影响和分子机制。综上，本项目以人群队列研究和动物试验研究为模型，互为提示、互为验证地揭示了环境内分泌干扰物母婴暴露对儿童肥胖的影响及其分子机制，为环境内分泌干扰物的危害鉴定提供了坚实的理论基础，为相关科学研究的开展提供了可靠的技术支撑，为儿童肥胖的预防和治疗提供了确切的科学依据。