Transplacental Transfer of Environmental Chemicals: Roles of Molecular Descriptors and Placental Transporters.

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.