BDE-47 Decreases Progesterone Levels in BeWo Cells by Interfering with Mitochondrial Functions and Genes Related to Cholesterol Transport

摘要

Polybrominated diphenyl ethers (PBDEs) have been reported to exert reproductive endocrine toxicity, but the mechanisms for this process remain unclear. Currently available studies have concentrated on the enzymatic reactions during steroidogenesis, but the results are not consistent. In this study, we explored the effects of 2,2',4,4'-tertrabromodiphenyl ether (BDE-47) on progesterone biosynthesis and the potential mechanisms in human placental choriocarcinoma cells. The results showed that BDE-47 decreased progesterone production in a dose-dependent manner but had no effect on key enzymes (Cypllal and 3 beta-HSD). BDE-47 exposure depolarized the mitochondrial membrane potential and downregulated adenosine triphosphate levels. The gene expression levels of Mfn2, Tspo, Atad3, Vdac1, Fis1, and Drp1, which are involved in mitochondrial dynamics and cholesterol transport, were disturbed. The demethylation of some CpG loci of mitochondrial biomarkers (Drp1, Opa1, Vdac2, and Atad3) was induced in the 1 mu M BDE-47 exposure group, but no methylation change was observed with 50 mu M treatment. Our findings unveiled that the reduction of progesterone synthesis induced by BDE-47 might be associated with cholesterol transportation, mitochondrial dynamics, and mitochondrial functions. These findings provide substantial data on the reproductive endocrine toxicity of PBDEs.