Disruption of thyroid hormone sulfotransferase activity by brominated flame retardant chemicals in the human choriocarcinoma placenta cell line, BeWo.
Brominated flame retardants (BFRs) have been shown to disrupt thyroid hormone (TH) homeostasis through multiple mechanisms, including inhibition of enzymes that regulate intracellular levels of THs, such as sulfotransferases (SULTs). The placenta plays a critical role in helping to maintain TH levels during fetal development and expresses SULTs. This is concerning given that disruption of TH regulation within the placenta could potentially harm the developing fetus. In this study, we investigated the effects of two polybrominated diphenyl ethers (PBDEs), two hydroxylated PBDEs, and 2,4,6-tribromophenol (2,4,6-TBP) on TH SULT activity in a choriocarcinoma placenta cell line (BeWo). BeWo cells were exposed to BFR concentrations up to 1 μM for 1-24 h to investigate changes in basal SULT activity and in mRNA expression of several TH regulating genes. 2,4,6-TBP was the most potent inhibitor of basal 3,3'-T2 SULT activity at all exposure durations, decreasing activity by as much as 86% after 24 h of exposure. BDE-99, 3-OH BDE-47, and 6-OH BDE-47 also decreased 3,3'-T2 SULT activity by 23-42% at concentrations of 0.5 μM and 1.0 μM following 24 h exposures. BDE-47 had no effect on SULT activity, and there was no observed effect of any BFR exposure on expression of SULT1A1, or thyroid nuclear receptors alpha or beta. This research demonstrates that total TH SULT activity in placental cells are sensitive to BFR exposure; however, the mechanisms and consequences have yet to be fully elucidated.
['Leonetti|Christopher P|CP|', 'Butt|Craig M|CM|', 'Stapleton|Heather M|HM|']
D045744:Cell Line, Tumor D002822:Choriocarcinoma D004104:Diiodothyronines D005260:Female D005411:Flame Retardants D055768:Halogenated Diphenyl Ethers D054879:Halogenation D006801:Humans D006900:Hydroxylation D010636:Phenols D010920:Placenta D011075:Polybrominated Biphenyls D011247:Pregnancy D011485:Protein Binding D015238:Sulfotransferases D013961:Thyroid Gland D013963:Thyroid Hormones
Thyroid hormones Sulfotransferase Flame Retardants BeWO Cell cultures