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.