Environmental Pollutant Benzo[a]pyrene Induces Recurrent Pregnancy Loss through Promoting Apoptosis and Suppressing Migration of Extravillous Trophoblast

Abstract

Objects. To investigate the effects of environmental pollutant benzo(a)pyrene (BaP) and its metabolite benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) on human trophoblasts and on murine miscarriages. 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.

Benzo[a]pyrene—Environmental Occurrence, Human Exposure, and Mechanisms of Toxicity

“…Epidemiological studies have shown that increased PAHs, including B[ a ]P, exposure could be connected with a variety of abnormalities, including lower serum progesterone levels, reduced fetal growth [ 170 ], and a higher risk of early miscarriage, which suggests a possible disturbing effect of these toxicants on the reproductive process [ 171 ]. Population analyses have also indicated that mice exposed to B[ a ]P showed depleted fetal weight, length, and head circumference; preterm delivery; birth defects; and reduced growth [ 172 ].…”

“…Population analyses have also indicated that mice exposed to B[ a ]P showed depleted fetal weight, length, and head circumference; preterm delivery; birth defects; and reduced growth [ 172 ]. Ye et al [ 171 ] recently investigated the effects of B[ a ]P and its metabolite, BPDE, on human trophoblasts and miscarriages in mice. They found a dose-dependent incidence of abnormal murine fetuses starting from a dose of B[ a ]P of 0.1 µg/kg; at a dose of 2 mg/kg, no fetus was developed.…”

Seasonality of Hypoplastic Left Heart Syndrome and Single Ventricle Heart in Poland in the Context of Air Pollution

“…Furthermore, it can also affect female reproductive health and pass through the placental barrier [ 49 ]. B(a)P can cause enhanced cell apoptosis and inhibited migration, leading to trophoblast dysfunction and pregnancy loss [ 50 ]. Its metabolites can also cause choriocarcinoma, intrauterine growth restriction and eclampsia [ 49 ].…”

BPDE, the Migration and Invasion of Human Trophoblast Cells, and Occurrence of Miscarriage in Humans: Roles of a Novel lncRNA-HZ09

“… 19 Dysfunctions of human trophoblast cells may lead to impaired uterine spiral artery rebuilding and trophoblast-related adverse pregnancy outcomes, such as miscarriage. 20 In our recent work, we found that human trophoblast cell lines HTR-8/SVneo 21 and Swan 71 20 , 22 cells treated with BPDE had higher levels of apoptosis and exhibited less proliferation, invasion, and migration. Human villous explants treated with BPDE also exhibited less migration and invasion.…”