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

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. 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 foetal side. The miRNAs significantly associated with chemicals were used to perform pathway enrichment analysis. 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 signalling and immune-related pathways. 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. During pregnancy, chemicals may pass differently from the mother to the developing foetus through the placenta. This study examined whether exposure to essential elements and persistent pollutants was associated with changes in circulating microRNA expression, small molecules that regulate gene activity. Blood samples from 95 mother–infant pairs enroled in the NEHO birth cohort were analysed. Chemical exposures and microRNA patterns were measured in both maternal and cord blood, and the effects of individual analytes and mixtures were investigated. The results showed that only a few microRNAs responded similarly in both compartments, whereas most displayed distinct maternal and cord blood responses. These findings suggest that the placenta is not only a barrier, but also an active regulator of early-life development. This research may help to identify early warning markers of environmental effects during pregnancy. Cosentini, Li Vigni et al. examine associations between essential elements, persistent organic pollutants and circulating miRNA profiles in 95 maternal–cord pairs. Prenatal exposure to chemical mixtures modulates distinct maternal and foetal miRNA responses.