Maternal cadmium, placental PCDHAC1, and fetal development

- Maternal cadmium is associated with restricted fetal growth.
- Placental PCDHAC1 expression is inversely associated with maternal cadmium.
- Placental PCDHAC1 expression is positively associated with fetal growth.
- Associations were strongest for those with lower methylation in the PCDHAC1 promoter.

Cadmium (Cd) is a ubiquitous environmental contaminant implicated as a developmental toxicant, yet the underlying mechanisms that confer this toxicity are unknown. Mother-infant pairs from a Rhode Island birth cohort were investigated for the potential effects of maternal Cd exposure on fetal growth, and the possible role of the PCDHAC1 gene on this association. Mothers with higher toenail Cd concentrations were at increased odds of giving birth to an infant that was small for gestational age or with a decreased head circumference. These associations were strongest amongst those with low levels of DNA methylation in the promoter region of placental PCDHAC1. Further, we found placental PCDHAC1 expression to be inversely associated with maternal Cd, and PCDHAC1 expression positively associated with fetal growth. Our findings suggest that maternal Cd affects fetal growth even at very low concentrations, and some of these effects may be due to the differential expression of PCDHAC1.