Impact of a prenatal exposure mixture of metals on DNA methylation-derived cell-type composition in cord blood

Le résumé fourni par la source

Abstract Metal(loid) exposure can exert immunotoxic effects, including changes in white blood cell proportions. The impact from metal exposure mixtures during pregnancy has not been examined in relation to cell-type composition at birth. Our aim was to evaluate the associations between a prenatal metal(loid) exposure mixture and cord blood DNA methylation-derived cell-type composition. We leveraged the PROGRESS birth cohort with measured prenatal immunotoxic metal(loid)s in blood (manganese, lead) and urine (arsenic, cadmium) and DNA methylation-derived cell-type composition from cord blood (n = 428). We used the novel Dirichlet Bayesian Weighted Quantile Sum regression to elucidate the association of metal mixtures on a compositional outcome with several DNA methylation-derived cell types: granulocytes (GR), CD4+ and CD8+ T-cells, B-cells, monocytes, natural killer (NK) cells, and nucleated red blood cells (nRBCs). We also conducted stratified analyses by fetal sex. We observed no associations in the overall population. In sex-stratified models, a one-quartile increase in metal mixture among the pregnant women carrying a female was associated with a 4.85% [95% credible intervals (CrI): 1.11%, 8.81%] increase in GR proportion, driven by arsenic. Conversely, a one-quartile increase in metal mixture in women carrying a male was marginally associated with a 3.44% (95% CrI: −7.08%, 0.37%; 80%CrI: −5.83%, −1.01%) decrease in GR proportion, driven by cadmium. We also observed marginal metal mixture associations with higher proportions of CD8+ T-cells in women carrying a male and lower proportion of NK cells and nRBCs in women carrying a female. Our findings suggest a potential differential metal mixture-cell composition associations given by fetal sex.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.