Placental Transcriptomic\nSignatures of Prenatal Phthalate\nExposure and Identification of Placenta-Brain Genes Associated with\nthe Effects of Phthalate Exposure on Neurodevelopment in Children

Prenatal exposure to phthalates may affect placental\nfunction and\nfetal development, but the underlying mechanisms are unclear. The\naim of our study was to explore the alterations in the placental transcriptome\nassociated with prenatal phthalate exposure and to further analyze\nwhether the placental–brain axis (PBA) genes play a mediating\nrole in the association between prenatal phthalate exposure and children’s\nneurodevelopment. We included 172 participants from the Ma’anshan\nBirth Cohort and collected data on seven phthalate metabolites in\nurine during pregnancy, placental tissue RNA-seq, and neurodevelopment\nof offspring. Bioinformatics analysis revealed that aberrant regulation\nof the placental transcriptome was associated with prenatal phthalate\nexposure. Exposure to phthalates during pregnancy was found to be\nassociated with neurodevelopmental delay in children aged 6, 18, and\n48 months using the multiple linear regression model. Meanwhile, employing\nmediation analysis, nine PBA genes were identified that mediate the\nassociation between exposure to phthalates during pregnancy and the\nneurodevelopment of children. Our study will provide a basis for potential\nmechanisms by which prenatal exposure to phthalates affects placental\nfunction and children’s neurodevelopment.