J Hazard Mater. 2025 Nov 4;500:140355. doi: 10.1016/j.jhazmat.2025.140355. Online ahead of print.
ABSTRACT
Phthalates, notably di-(2-ethylhexyl) phthalate (DEHP), are pervasive endocrine-disrupting chemicals used in consumer products. Prenatal DEHP exposure has been linked to adverse developmental and immune outcomes, yet the molecular mechanisms remain unclear. We conducted a prospective study using cord blood transcriptomics to examine associations between maternal DEHP exposure levels and neonatal gene expression. Maternal urinary DEHP metabolites were measured in the Taiwan Maternal and Infant Cohort Study, and RNA sequencing was performed on cord blood from 125 newborns. After adjustment for maternal and perinatal covariates, pathway enrichment analysis showed negative associations with key metabolic pathways (fatty acid, amino acid, and energy metabolism, and steroid biosynthesis) and immune pathways (antigen processing and presentation, T cell receptor signaling, and natural killer cell-mediated cytotoxicity). At the gene level, RCOR2 expression increased while WNT7A decreased in relation to ΣDEHP exposure. Immune cell deconvolution revealed inverse correlations of ΣDEHP with CD8⁺ T cells and activated NK cells, and a positive association with undifferentiated macrophages, suggesting immune dysregulation. These findings indicate that maternal DEHP exposure may disrupt immune composition and metabolic programming at the transcriptomic level in the offspring. Such alterations during a critical developmental window may predispose children to long-term immunological and metabolic dysfunction, underscoring the need for stricter environmental regulations and further research into the developmental impacts of phthalates.
PMID:41205498 | DOI:10.1016/j.jhazmat.2025.140355
