产前邻苯二甲酸盐暴露的胎盘转录组学特征以及与邻苯二酸盐暴露对儿童神经发育影响相关的胎盘脑基因的鉴定

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

产前邻苯二甲酸盐暴露的胎盘转录组学特征以及与邻苯二酸盐暴露对儿童神经发育影响相关的胎盘脑基因的鉴定

Authors: Jiawen Ren, Yifan Wang, Yimin Zhang, Heyue Jin, Jingjing Cheng , Fangbiao Tao, Yumin Zhu.

Source:  Environ Sci Technol.2024 Oct 11.

 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: mediation effects; neurodevelopment; phthalates; placenta; transcriptomics.

摘要

产前暴露于邻苯二甲酸盐可能会影响胎盘功能和胎儿发育，但其潜在机制尚不清楚。本研究的目的是探讨与产前邻苯二甲酸酯暴露相关的胎盘转录组的改变，并进一步分析胎盘-脑轴（PBA）基因是否在产前邻苯二甲酸酯暴露与儿童神经发育之间的关联中起中介作用。我们纳入了来自马鞍山出生队列的 172 名参与者，并收集了妊娠期尿液中 7 种邻苯二甲酸酯代谢物、胎盘组织 RNA-seq 和后代神经发育的数据。生物信息学分析显示，胎盘转录组的异常调节与产前邻苯二甲酸酯暴露有关。使用多元线性回归模型发现怀孕期间接触邻苯二甲酸盐与 6 、 18 和 48 个月儿童的神经发育迟缓有关。同时，采用中介分析，鉴定出 9 个 PBA 基因，这些基因介导怀孕期间接触邻苯二甲酸盐与儿童神经发育之间的关联。我们的研究将为产前接触邻苯二甲酸盐影响胎盘功能和儿童神经发育的潜在机制提供基础。

关键词：中介效应；神经发育；邻苯二甲酸盐；胎盘；转录组学。