Transplacental transfer mechanism of organochlorine pesticides: An in vitro transcellular transport study

•Placenta actively transports xenobiotic out of the fetus with higher efflux.•No enantiomer-specific transfer observed in the in vitro model.•Most of the OCPs transported across the BeWo monolayer by simple diffusion.•ABC transporter proteins have redundancy in substrates for active transport.•Transplacental efficiency could be used to improve PBPK models. Recent studies show that, even after being banned for agricultural applications for over 30 years, organochlorine pesticides (OCPs), including hexachlorocyclohexanes (HCHs) and dichlorodiphenyltrichloroethane (DDT) and its metabolites (DDXs), can still be found in various biological matrices and pose a potential hazard to the fetus in the womb. This study aimed to investigate the possible transplacental transfer mechanism of OCPs using an in vitro placental model. The results showed that for HCHs and DDXs, the placenta had a potential protection mechanism for the fetus by having higher efflux than intake active transport efficiency to transfer the xenobiotic out of the fetal circulation. No enantiomer-specific transport was observed for the chiral OCPs in vitro, hints simple diffusion played the major role in the transplacental transfer. Metabolic and transporter inhibitors were applied in the transepithelial transport experiment to evaluate the role that major transporting protein played in the active efflux process. The ATP production inhibitors were observed to have significant inhibition on transfer, proving the hypothesis that active transport participates in the transplacental transport of OCPs in humans. Multiple transporters contributed simultaneously in the active transport for the OCPs. In this study, we could confirm that the transplacental transfer of OCPs is a combination of simple diffusion and active transport. ATP-binding cassette (ABC) superfamily transporters on the placenta contribute in the active transport. These findings could improve the understanding of the mechanisms of transplacental transfer of the OCPs.