Effects of novel brominated flame retardants on steroidogenesis in primary porcine testicular cells.
Brominated flame retardants are chemicals with fire quenching properties which are extensively used in manufacturing. Historically, less regulated use of legacy brominated flame retardants (BFRs) for a number of years has resulted in ubiquitous contamination of the environment. As a result, some of the more persistent BFRs have been phased out and are being replaced by a next generation of brominated compounds for which there is little toxicological data. The study investigated effects of 2-ethylhexyl tetrabromobenzoate (TBB), 1,2,5,6-tetrabromocyclooctane (TBCO), and bis-(2-ethylhexyl) tetrabromophthalate (TBPH)on steroidogenesis in a porcine primary testicular cell model. TBB did not affect sex-steroid production in this cell model; rather the data suggest a flux towards synthesis of aldosterone and cortisol via up-regulation of CYP21A2. At the greatest concentrations of TBCO and TBPH tested greater production of sex hormones testosterone (T) and estradiol (E2) was observed. Effects were mediated by regulation of multiple molecular targets in the steroidogenesis pathway; CYP11A in the case of TBPH and CYP17A1 in the case of TBCO. This investigation is the first of its kind to use a testicular mixed population cell model to investigate mechanism(s) of action of three chemically diverse compounds currently used in commercial fire retardants.
Rishikesh
R
Mankidy
Bibhuti
B
Ranjan
Ali
A
Honaramooz
John P
JP
Giesy
D000818:Animals; D034242:Cyclooctanes / Q000633:toxicity; D004958:Estradiol / Q000096:biosynthesis*; D005411:Flame Retardants / Q000633:toxicity*; D006842:Hydrocarbons, Brominated / Q000633:toxicity; D008297:Male; D010795:Phthalic Acids / Q000633:toxicity; D013552:Swine; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis*; D059467:Transcriptome
C540596:1,2,5,6-tetrabromocyclooctane; D034242:Cyclooctanes; D005411:Flame Retardants; D006842:Hydrocarbons, Brominated; D010795:Phthalic Acids; C016132:tetrabromophthalic acid; D013739:Testosterone; D004958:Estradiol