Placental Lesions in CD-1 Mouse Placenta Following Gestational Exposure to Perfluorooctanoic Acid (PFOA) or Hexafluoropropylene Oxide Dimer Acid (HFPO-DA or GenX)

Abstract

Exposure to certain per- and polyfluoroalkyl substances (PFAS) is associated with adverse pregnancy outcomes in mice and humans. These adverse outcomes are suspected to be due to exposure-related toxic effects on the placenta. This study was designed to more explicitly define the effects of selected PFAS on all regions of the placenta of pregnant CD-1 mice. Pregnant CD-1 mice were gavaged with perfluorooctanoic acid (PFOA; 1 or 5 mg/kg-d) or hexafluoropropylene oxide dimer acid (GenX; 2 or 10 mg/kg/day) from embryonic day (E) 1.5 to E17.5. Exposure to either PFOA or GenX resulted in higher placenta weights and lower placental efficiency (embryo:placenta weight ratio). Light microscopic evaluation of the placentae revealed treatment-associated lesions in the decidua, junctional zone, and labyrinth. The reduced placental efficiency and microscopic findings were consistent with maternal vascular malperfusion. With few exceptions, there were no differences between the effects of PFOA when compared with GenX, except for increased necrosis of spongiotrophoblasts in the high-dose PFOA-treated group. Taken together, these findings suggest both PFOA and GenX cause multiple pathological changes at the microscopic and tissue level of the placenta consistent with adverse maternal-fetal health outcomes.