Effects of an environmental chemical mixture on early-stage embryo development: In vitro evidence from human embryonic stem cells

Environmental chemicals are known risk factors for adverse pregnancy outcomes. However, the effects of environmentally relevant concentrations of chemical mixtures are less studied. This study investigated the effects of a mixture containing 23 chemicals reported in blood samples of Nunavik pregnant women, termed the Nunavik Chemical Mixture (NCM), on embryo development using human embryonic stem cells (hESCs). hESCs were exposed to 0-100X of NCM (X is the sum of geometric mean concentrations of NCM's components) for 24 h and 6 d Cell viability, apoptosis, stress response, cell cycle, cytoskeleton, autophagy, and expression of lineage marker genes/proteins were measured after exposures. NCM decreased cell viability and adhesion, induced apoptosis, disrupted the cell cycle, and altered the expression of cytoskeleton, autophagy proteins, and lineage marker genes/proteins in a dose-dependent manner. These results suggested that NCM affected embryo development, leading to potential adverse pregnancy outcomes if it occurs in vivo. Moreover, the effects caused by NCM were different from those caused by the same doses of MeHg alone that we previously found, indicating potential interactions among components within the mixture. Our results highlight the importance of considering the potential combined effects of chemical mixtures when assessing health risks in populations exposed to various environmental chemicals.