Disruption of thyroid hormone sulfotransferase activity by brominated flame retardant chemicals in the human choriocarcinoma placenta cell line, BeWo

Autor: Christopher Leonetti, Craig M. Butt, Heather M. Stapleton
Rok vydání: 2018
Předmět:
0301 basic medicine
Thyroid Hormones
medicine.medical_specialty
Sulfotransferase
Environmental Engineering
Halogenation
Diiodothyronines
Placenta
Health
Toxicology and Mutagenesis
Polybrominated Biphenyls
Thyroid Gland
010501 environmental sciences
Hydroxylation
01 natural sciences
Article
03 medical and health sciences
Polybrominated diphenyl ethers
Phenols
Pregnancy
Cell Line
Tumor
Internal medicine
Halogenated Diphenyl Ethers
medicine
Humans
Environmental Chemistry
Choriocarcinoma
Flame Retardants
0105 earth and related environmental sciences
Fetus
Chemistry
Public Health
Environmental and Occupational Health
General Medicine
General Chemistry
medicine.disease
Pollution
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Nuclear receptor
Brominated flame retardant
Female
Sulfotransferases
Protein Binding
Hormone
Zdroj: Chemosphere. 197:81-88
ISSN: 0045-6535
Popis: 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.
Databáze: OpenAIRE
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