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

Abstract

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.

Prenatal Exposure to Emerging Plasticizers and Synthetic Antioxidants and Their Potency to Cross Human Placenta

“…Relatively high TTEs (i.e., >1.0) were determined for BHT-COOH (1.30), BHT-Q (1.32), BHT-quinol (1.17), DMS (1.87), and MBB (2.14), whereas other chemicals of interest had TTEs less than 1.0 (Table , Figure ). For comparison, previous studies have reported that the TTEs of major per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls, and organochlorine pesticides were generally less than 1.0, while the major PBDE congeners and selected PFAS had TTEs greater than 1.0, although the measured TTEs for the same chemical could exhibit large variations between studies. , Indeed, the only available TTE study for BHT reported a mean value of 0.22 (Table S2), far less than what we determined in the present study (i.e., 0.95) …”

“…The chemical composition profiles also exhibited large differences between maternal and cord serum; i.e., maternal serum contained larger proportions of 2,4-D t BP and DPG compared with cord serum, whereas the latter contained elevated compositions of BHT metabolites (Figure B). A recent meta-analysis indicated that maternal levels of environmental chemicals, most of which were lipophilic, could overall exert a significant influence on their levels in cord blood . Our results suggested that other than maternal levels there could be additional factors influencing the levels of target chemicals in fetal side.…”

A Comprehensive Non-targeted Analysis Study of the Prenatal Exposome

“…The partitioning of chemicals between cord and maternal blood has also been described as a concentration ratio in previous studies. [36][37][38] Previous studies have shown that the partitioning behavior of chemicals between maternal and cord blood is related to the chemicals' physicochemical properties 39,40 and to certain physiological parameters that can affect the placenta, such placental aging 41 and gestational diabetes 42 . In an attempt to understand the parameters determining RCM we used a linear regression model to assess its relationship to physicochemical properties and physiological parameters.…”

Nano-TiO2retarded fetal development by inhibiting transplacental transfer of thyroid hormones in rats

“…A developing fetus is especially vulnerable to toxicants, raising significant concerns over children's health. [1][2][3] The most common developmental abnormalities are attributed to maternal exposure to toxins. 4 Recognizing the increasing applications of nanoparticles (NPs) in commercial products, evidence accumulates that certain NPs can overcome the placental barrier and pose adverse effects on fetal development.…”

“…Although the placenta can protect the fetus against certain xenobiotics, many small xenobiotic molecules can still cross the placenta via simple diffusion and disturb the homeostasis of placental metabolism, 15,16 compromising placental protective features and even fetal health. 3 For example, nTiO 2 can migrate into CD-1ICR mice uteruses, making the placenta and fetus the major targets of developmental toxicity after prenatal exposure to nTiO 2 (6.5 nm, anatase, 25, 50, and 100 mg kg −1 , oral exposure) from gestation days (GDs) 0 to 17. 11 nTiO 2 may interfere with the placental permeability of Ca 2+ , leading to reduced ossification through decreasing calcium and zinc in the fetus.…”