Pregnant women are routinely exposed to complex mixtures of environmental chemicals, yet their impact on fetal development depends on how much reaches the fetal compartment. The placenta regulates this — but is not impermeable: chemicals can cross it, accumulate in its tissue, or be actively transported to the fetus. Mechanisms governing inter-individual variability in this transfer are poorly understood, and no study has tested whether placental transporter expression is a key determinant. PLACEXPO asks: does variability in placental active transport gene expression explain why identical prenatal exposures lead to different fetal transfer and growth outcomes?
Embedded within the INSULIN mother-child cohort (2021–ongoing; Hospital Joan XXIII, Tarragona), directed by the PI of PLACEXPO, the project builds on PREGO (placental and maternal chemical exposome) and FEMME (placental metabolic transformation) to address the missing piece: cord serum chemical profiling to calculate compound-specific transfer ratios, and transporter gene expression quantification in placental tissue. Preliminary data from 23 INSULIN dyads show physicochemical properties cannot predict placental partitioning — direct motivation for the active transport hypothesis.
Three objectives structure the project: (i) quantify >600 environmental chemicals in cord serum and calculate compound-specific placental transfer ratios; (ii) characterize expression of five placental active transporter genes (ABCB1, ABCG2, ABCC2, SLCO2B1, SLC22A8) by RT-qPCR; and (iii) integrate chemical, molecular and clinical data to test whether transporter expression determines inter-individual variability in placental transfer and mediates its consequences for fetal growth. PLACEXPO will deliver the first population-level framework linking the placental chemical exposome, its molecular determinants and fetal growth — positioning the placenta as an active regulator of prenatal chemical risk.
