基于出生队列研究孕期PAEs暴露对子代神经行为发育的影响及PPARγ基因甲基化调控机制

Phthalate esters (PAEs) are a group of persistent organic pollutants widely present in the environment, and have certain neurotoxic effects. However, studies on the effects of intrauterine PAE exposure on the neurodevelopment of offspring are still scarce and the mechanism of action is also unclear. In this project, we relied on the established Tongji birth cohorts to study the effects of pregnancy PAE exposure on the neurodevelopment of offspring and its mechanism of action. By measuring the levels of PAE metabolites in the urine of pregnant women in the first, second, and third trimesters of pregnancy, the levels and distribution characteristics of PAE exposure were precisely evaluated. The neurobehavioral development of the offspring at 3 years of age was assessed, the effects of PAE exposure at different stages of pregnancy on childhood neurodevelopment were analyzed, and the exposure–response relationship was determined. At the same time, combined with the peroxisome proliferator-activated receptor gamma methylation levels in the placenta of the pregnant women, the epigenetic mechanism by which pregnancy PAE exposure causes neurodevelopment toxicity in offspring was further explored. The results provide basic data for accurate and comprehensive assessments of the effects of intrauterine PAE exposure on the neurodevelopment of offspring, and provide new references for further study on the toxic mechanism of PAEs.

邻苯二甲酸酯（Phthalate esters, PAEs）是一类广泛存在于环境中的持久性有机污染物，具有一定的神经毒性作用。但有关宫内PAEs暴露对子代神经发育影响的研究还很缺乏，其作用机制也不明确。本项目依托已经建立的同济出生队列，系统研究孕期PAEs暴露对子代神经行为发育的影响及其甲基化作用机制。通过测定母亲孕早、孕中、孕晚期尿液中PAEs代谢产物含量，来精确评估PAEs的暴露水平和分布特征；随访并评估子代3岁时的神经行为发育，明确孕期不同阶段PAEs暴露对儿童神经发育的影响；同时结合孕妇胎盘PPARγ甲基化水平检测，进一步阐明孕期PAEs暴露致子代神经发育毒性的表观遗传学机制。研究结果为准确、全面地评估宫内PAEs暴露对子代神经发育的影响提供基础资料，为深入开展PAEs的毒性机制研究提供新的参考。

邻苯二甲酸酯（Phthalate esters, PAEs）是一类广泛存在于环境中的持久性有机污染物，具有一定的神经毒性作用。但有关宫内PAEs暴露对子代神经发育影响的研究还很缺乏，其作用机制也不明确。本项目基于在2018年10月在鄂州市妇幼保健院建立的出生队列，至今共招募孕妇800多名，发放调查问卷，并收集生物样本。检测了尿液中8种PAEs的代谢物及血液中的甲状腺相关激素。并初步完成了379名配对儿童的随访，由儿保科医生对新生儿神经行为(NBNA)发育进行评分。研究结果发现，孕期DEHP的代谢物、MnBP可以上调血液中TSH的浓度(β= 4.25, 95% CI= 0.32,8.18；β= 5.12, 95% CI= 1.25,8.99)，而MEP与FT4（β= -1.26, 95% CI= -2.34,-0.18）、MnBP与TT3（β= -2.62, 95% CI= -3.17,-2.07）呈负相关关系。研究还发现，与孕期低MMP、MEP、MBzP、MEHP、∑PAEs组相比，高MMP、MEP、MBzP、MEHP、∑PAEs组新生儿神经行为能力得分较低。本课题系统研究孕期PAEs暴露对子代神经行为发育的影响及其甲状腺相关激素作用机制，为深入开展PAEs的毒性机制研究提供新的参考。