School of Environment and Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, China.
College of Pharmacy, Jinan University, Guangzhou 510632, China.
Environ Sci Technol. 2021 Jan 5;55(1):519-528. doi: 10.1021/acs.est.0c06778. Epub 2020 Dec 9.
Transplacental transfer of environmental chemicals results in direct risks to fetal development. Although numerous studies have investigated transplacental transfer efficiencies (TTEs) of environmental chemicals, the underlying mechanisms and influencing factors remain poorly understood. The present study aims to synthesize a current state of knowledge on the TTEs of major environmental chemicals and explore the roles of chemicals' molecular descriptors and placental transporters in the transplacental transfer. The results indicate great variations in TTEs (median: 0.29-2.86) across 51 chemicals. Chemical-dependent TTEs may partially be attributed to the influences of chemicals' molecular descriptors. Predictive models based on experimental TTEs and 1790 computed molecular descriptors indicate that a very limited number of molecular descriptors, such as the topological polar surface area, may substantially influence and efficiently predict chemicals' TTEs. In addition, molecular docking analyses were conducted to determine the binding affinities between 51 chemicals and six selected transporters, including BCRP, MDR1, hENT1, FRα, SERT, and MRP1. The results reveal transporter- and chemical-dependent binding affinities. Therefore, our study demonstrates that molecular descriptors and placental transporters, among a variety of other factors, can play important roles in the transplacental transfer of environmental chemicals. However, the underlying mechanisms and several important knowledge gaps identified herein require further investigations.
环境化学物质经胎盘转移会对胎儿发育造成直接风险。虽然已有大量研究调查了环境化学物质的经胎盘转移效率（TTE），但其潜在机制和影响因素仍知之甚少。本研究旨在综合目前关于主要环境化学物质 TTE 的知识，并探讨化学物质分子描述符和胎盘转运体在经胎盘转移中的作用。结果表明，51 种化学物质的 TTE 差异很大（中位数：0.29-2.86）。化学物质依赖性 TTE 可能部分归因于化学物质分子描述符的影响。基于实验 TTE 和 1790 种计算分子描述符的预测模型表明，少数分子描述符（如拓扑极性表面积）可能会显著影响并有效地预测化学物质的 TTE。此外，还进行了分子对接分析，以确定 51 种化学物质与 6 种选定转运体（BCRP、MDR1、hENT1、FRα、SERT 和 MRP1）之间的结合亲和力。结果揭示了转运体和化学物质依赖性的结合亲和力。因此，本研究表明，分子描述符和胎盘转运体（以及其他多种因素）可在环境化学物质的经胎盘转移中发挥重要作用。然而，其中确定的潜在机制和一些重要的知识空白仍需要进一步研究。
