Disruption
of the Hormonal Network and the Enantioselectivity
of Bifenthrin in Trophoblast: Maternal–Fetal Health Risk of
Chiral Pesticides
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Abstract
Endocrine-disrupting
chemicals (EDCs) can interfere with normal
hormone signaling to increase health risks to the maternal–fetal
system, yet few studies have been conducted on the currently used chiral
EDCs. This work tested the hypothesis that pyrethroids could enantioselectively
interfere with trophoblast cells. Cell viability, hormone secretion,
and steroidogenesis gene expression of a widely used pyrethroid, bifenthrin
(BF), were evaluated <i>in vitro</i>, and the interactions of BF enantiomers
with estrogen receptor (ER) were predicted. At low or noncytotoxic
concentrations, both progesterone and human chorionic gonadotropin
secretion were induced. The expression levels of progesterone receptor
and human leukocyte antigen G genes were significantly stimulated.
The key regulators of the hormonal cascade, GnRH type-I and its receptor,
were both upregulated. The expression levels of selected steroidogenic
genes were also significantly altered. Moreover, a consistent enantioselective
interference of hormone signaling was observed, and <i>S</i>-BF had greater effects than <i>R</i>-BF. Using molecular
docking, the enantioselective endocrine disruption of BF was predicted
to be partially due to enantiospecific ER binding affinity. Thus,
BF could act through ER to enantioselectively disturb the hormonal
network in trophoblast cells. These converging results suggest that
the currently used chiral pesticides are of significant concern with
respect to maternal–fetal health