Prenatal environmental exposures and distinct microRNA patterns in maternal and cord serum

Background Environmental exposures during pregnancy can influence crosstalk between the maternal and foetal compartments, eliciting distinct yet coordinated adaptive responses at the placental interface. MiRNAs act as key mediators, translating environmental stress into post-transcriptional regulatory signals. Methods This study investigates the effects of prenatal exposure, examining associations between essential elements (EEs), persistent organic pollutants (POPs), and circulating miRNA profiles in 95 maternal–cord pairs from the NEHO birth cohort. To this aim, single-chemical and bWQS models were perfomed in both maternal and fetal side. The miRNAs significantly associated with chemicals were used to perform pathway enrichment analysis. Results Single-chemical regression models identified distinct sets of miRNAs altered by EEs or POPs in the maternal and cord compartments, while mixture analysis (bWQS) confirmed these associations and revealed both shared and compartment-specific miRNA signatures. Pathway enrichment analysis of miRNA-target genes revealed a side characteristic modulation of key signaling and immune-related pathways. Conclusions These findings demonstrate that prenatal exposure to chemical mixtures modulates distinct maternal and foetal miRNA responses, highlighting the placenta’s dual role as a selective barrier and active regulator of foetal programming.