Analogue-Specific Transplacental Transfer of Organophosphate Flame Retardants in ICR Mouse Mediated by Active...

Prenatal exposure to organophosphate flame retardants (OPFRs) may pose potential health risks to offspring. While prior studies have demonstrated that OPFRs can be transferred from mothers to fetuses, the mechanism underlying transplacental transfer remains unclear. The pregnant ICR mouse and JAR cell (a monolayer model), in combination with molecular docking, were used to explore the underlying mechanism. OPFRs were rapidly metabolized into diester metabolites following oral gavage in the ICR mouse, with considerable concentrations detected in maternal serum, amniotic fluid, and placenta, as well as fetus within 3 h. After 6 h, the accumulation ratios of OPFRs between the mother and fetus exhibited a parabolic relationship with log K_OW. Oral exposure resulted in a decrease in interstitial cells in the decidua and an expansion of vascular systems in the labyrinthine area. RT-qPCR analysis revealed upregulated expression levels of transporter mRNA in the placenta, suggesting a protective mechanism characterized by greater efflux than influx transport efficiency. Metabolic inhibitors applied during in vitro transepithelial transport experiments using the JAR cells significantly reduced the transport efficiency, indicating that active transport facilitated the transplacental transport of aryl-OPFRs, with reductions exceeding 50%. Molecular docking analysis indicated that aryl-OPFRs exhibited greater binding affinities to placental transporters compared to other types of OPFRs, with more bonding interactions. These findings offer new insights into the potential health impacts of OPFR exposure and highlight the importance of elucidating their transplacental transport mechanisms.