Abstract
Methods The implantation sites, fetus resorption, and abnormal fetuses were studied in pregnant mice treated with different doses of BaP by oral gavage from day 1 to day 10 of gestation. Additionally, apoptosis and related signaling pathway, and the migration and invasion of trophoblasts, were assessed before and after exposure of BPDE in Swan 71 trophoblast cell. Besides, the migration and invasion, and its related signaling pathway, were assessed in villi obtained from women. Results We observed a concentration-dependent incidence of abnormal murine fetuses, beginning with 0.1 mg/kg BaP; with a BaP concentration of 2 mg/kg, no fetuses developed. Correspondingly, a BPDE concentration-dependent apoptosis of human trophoblasts. Beginning with 0.5 μM BPDE exposure, Bax/Caspase-3 were increased and Bcl-2 decreased. Furthermore, BPDE also inhibited, in a dose-dependent manner, the migration of villous explants from elective abortion women, consistent with the reduced migration of villous explants from women with recurrent pregnancy loss (RPL), and reduced the cell immigration in Swan 71 trophoblasts, in a dose-dependent manner measured by transwell assays. Conclusions Our study results provide mechanistic insight to the effect of BPDE on trophoblast dysfunction through enhanced cell apoptosis and inhibited migration, providing further experimental evidence to the causative links between BaP exposure and PRL.
Highlights
There is a growing concern about the effects of environment endocrine-disrupting chemical (EDC) exposure on the human reproduction
Since apoptosis is much more evident in the human villous tissue from patients with recurrent pregnancy loss (RPL), we investigated the effect of BPDE on the apoptosis of trophoblasts using Swan 71 cell line
Previous studies in its reproductive toxicity have mainly focused on the ovarian disorders, endometrial cell apoptosis, and decidualization [10, 20, 21]
Summary
There is a growing concern about the effects of environment endocrine-disrupting chemical (EDC) exposure on the human reproduction. Studies have found that some negative pregnancy outcomes may be related to representative polycyclic aromatic hydrocarbons (PAH) exposure [1]. BaP is activated by the aromatic hydrocarbon receptor-induced cytochrome P4501A1 and epoxide hydrolase and metabolized as carcinogenic benzo[a]pyren-7,8-dihydrodiol-9,10-epoxide (BPDE) [4]. Epidemiological studies have found that exposure to elevated levels of PAHs may be associated with lower serum levels of progesterone, reduced fetal growth [5], and higher risk of early miscarriage [6], implying it may interfere in the reproductive process [7]. The population analysis suggested that BaP exposure was associated with the reduced fetal birth weight and length, head circumference, preterm birth, congenital anomalies, and growth restriction [3, 8, 9]
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