Institution of Environmental Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China.
Institution of Environmental Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China; Department of Preventive Medicine, School of Medicine, Hangzhou Normal University, Hangzhou 310036, China.
Environ Int. 2020 Feb;135:105402. doi: 10.1016/j.envint.2019.105402. Epub 2019 Dec 20.
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.
最近的研究表明，即使在被禁止用于农业应用 30 多年后，有机氯农药（OCPs），包括六氯环己烷（HCHs）和滴滴涕（DDT）及其代谢物（DDXs），仍然可以在各种生物基质中被发现，并对子宫内的胎儿构成潜在威胁。本研究旨在利用体外胎盘模型研究 OCPs 可能的胎盘转移机制。结果表明，对于 HCHs 和 DDXs，胎盘对胎儿具有潜在的保护机制，其外排比摄入的主动转运效率更高，从而将外来物质从胎儿循环中转移出去。体外对手性 OCPs 没有观察到对映体特异性转运，提示简单扩散在胎盘转移中起主要作用。在跨上皮转运实验中应用代谢和转运蛋白抑制剂来评估主要转运蛋白在主动外排过程中的作用。观察到 ATP 产生抑制剂对转运有显著抑制作用，证明了主动转运参与了 OCPs 在人体中的胎盘转运的假说。多种转运蛋白同时参与 OCPs 的主动转运。在这项研究中，我们可以确认 OCPs 的胎盘转移是简单扩散和主动转运的结合。胎盘上的 ABC 超家族转运蛋白参与主动转运。这些发现可以提高对 OCPs 胎盘转移机制的理解。
