产前邻苯二甲酸酯（PAEs）暴露致胎盘转录发生异常调控，且胎盘-脑轴基因可能中介产前PAEs暴露和儿童神经发育关联

Placental Transcriptomic Signatures of Prenatal Phthalate Exposure and Identification of Placenta-Brain Genes Associated with the Effects of Phthalate Exposure on Neurodevelopment in Children

产前PAEs暴露的胎盘转录组特征及PAEs暴露影响儿童神经发育相关的胎盘-脑轴基因鉴定

Author: Jiawen Ren, Yifan Wang, Yimin Zhang, Heyue Jin, Jingjing Cheng, Fangbiao Tao,* and Yumin Zhu

Source: Environmental Science & Technology

DOI: 10.1021/acs.est.4c04082

Abstract

Prenatal exposure to phthalates may affect placental function and fetal development, but the underlying mechanisms are unclear. The aim of our study was to explore the alterations in the placental transcriptome associated with prenatal phthalate exposure and to further analyze whether the placental−brain axis (PBA) genes play a mediating role in the association between prenatal phthalate exposure and children’s neurodevelopment. We included 172 participants from the Ma’anshan Birth Cohort and collected data on seven phthalate metabolites in urine during pregnancy, placental tissue RNA-seq, and neurodevelopment of offspring. Bioinformatics analysis revealed that aberrant regulation of the placental transcriptome was associated with prenatal phthalate exposure. Exposure to phthalates during pregnancy was found to be associated with neurodevelopmental delay in children aged 6, 18, and 48 months using the multiple linear regression model. Meanwhile, employing mediation analysis, nine PBA genes were identified that mediate the association between exposure to phthalates during pregnancy and the neurodevelopment of children. Our study will provide a basis for potential mechanisms by which prenatal exposure to phthalates affects placental function and children’s neurodevelopment.

Keywords: phthalates, placenta, transcriptomics, neurodevelopment, mediation effects

摘要

产前邻苯二甲酸酯（phthalates，PAEs）暴露可能对胎盘功能以及胎儿发育产生影响，但其潜在机制尚不清楚。本研究旨在探讨与产前PAEs暴露相关的胎盘转录组改变，并进一步分析胎盘-脑轴（PBA）基因是否中介产前PAEs暴露与儿童神经发育的关联。基于马鞍山优生优育队列，本研究纳入172名参与者，并进一步获得她们孕期尿液中7种PAEs代谢物、胎盘组织RNA-seq以及子代神经发育的数据。生物信息学分析表明，胎盘转录组的异常调控与产前PAEs暴露相关。利用多元线性回归模型发现，产前PAEs暴露与6月龄、18月龄和48月龄儿童的神经发育迟缓相关。同时，通过中介分析，鉴定出9个PBA基因在产前PAEs暴露与儿童神经发育关联中起到了中介作用。我们的研究将为产前PAEs暴露影响胎盘功能和儿童神经发育的潜在机制提供依据。