Oral Co-Exposures to zinc oxide nanoparticles and CdCl2 induced maternal-fetal pollutant transfer and embryotoxicity by damaging placental barriers

Synergistic toxicity from multiple environmental pollutants poses greater threat to humans, especially to susceptible pregnant population. Here we evaluated combined toxicity from environment pollutants zinc oxide nanoparticles (ZnO NPs) and cadmium chloride (CdCl2) using two pregnant mice models established by oral administration during peri-implantation or organogenesis period. We found that exposures to combined pollutants only at organogenesis stage induced higher fetal deformity rate compared to co-exposures at peri-implantation stage. We further discovered that surface charge of ZnO NPs were modified after Cd2+ adsorption and the resulting nanoadducts caused more severe damages in placental barriers by causing shed endothelial cells and decreased expressions of tight junction proteins ZO1, occludin, claudin-4 and claudin-8. These cellular and molecular events enhanced maternal-fetal transfer of both pollutants and aggravated embryotoxicity. Our findings help elucidate synergistic embryotoxicity by nanoparticle/pollutant adducts and establish proper safety criteria for pregnant population in an era that nanotechnology-based products are widely used.