Maternal Exposure to Quaternary Ammonium Disinfectants: Transplacental Transfer and Adverse Effects on Placental Function

Abstract

Quaternary ammonium disinfectants (QACs) are being increasingly used since the COVID-19 pandemic, however, their potential impacts on sensitive populations (e.g., pregnant populations and developing fetuses) remain largely unexplored. In this study, we combined human biomonitoring with in vivo models (including rat uterine perfusion and oral administration in mice) and an in vitro model (human placental trophoblast BeWo cell line) to evaluate gestational exposure, the transplacental transport, and the toxic effects of QACs on placenta function. QACs are frequently detected in human maternal and cord blood/serum, revealing widespread gestational exposure and potential health effects. The molecular structure and lipid solubility affect the transplacental transfer of QACs. Using RT–qPCR, Western blotting, immunofluorescence staining of rat placenta, siRNA-mediated knockdown in BeWo cells, and molecular docking analysis, we demonstrated that organic cation/carnitine transporters (OCTN1/2) are involved in the transplacental transfer of QACs. QACs exhibit stronger acute cytotoxicity (e.g., 3.75 μM for C10DDAC) than well-recognized reproductive toxicants (e.g., TCS, PFOS, PFOA and MEHP). Exposure to nonlethal concentrations of QACs disrupts the expression of genes involved in cell differentiation and placental vascular development and dysregulates progesterone release in BeWo cells. Together, these findings suggest a mechanistic pathway through which ubiquitous disinfectants reach the fetus and impair placental function, highlighting the urgent need to re-evaluate their use during pregnancy to prevent exposure and health risks to the developing fetus.