Effects of novel brominated flame retardants on steroidogenesis in primary porcine testicular cells

Rishikesh Mankidy; Bibhuti Ranjan; Ali Honaramooz; John P. Giesy

doi:10.1016/j.toxlet.2013.10.018

Effects of novel brominated flame retardants on steroidogenesis in primary porcine testicular cells

Rishikesh Mankidy, Bibhuti Ranjan, Ali Honaramooz, John P. Giesy

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

38 Citations (Scopus)

Abstract

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. © 2013 Elsevier Ireland Ltd.

Original language	English
Pages (from-to)	141-146
Journal	Toxicology Letters
Volume	224
Issue number	1
DOIs	https://doi.org/10.1016/j.toxlet.2013.10.018
Publication status	Published - 3 Jan 2014

Research Keywords

BFR
In vitro steroidogenesis
NBFR
TBB
TBCO
TBPH

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title = "Effects of novel brominated flame retardants on steroidogenesis in primary porcine testicular cells",

abstract = "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. {\textcopyright} 2013 Elsevier Ireland Ltd.",

keywords = "BFR, In vitro steroidogenesis, NBFR, TBB, TBCO, TBPH",

author = "Rishikesh Mankidy and Bibhuti Ranjan and Ali Honaramooz and Giesy, {John P.}",

year = "2014",

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doi = "10.1016/j.toxlet.2013.10.018",

language = "English",

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pages = "141--146",

journal = "Toxicology Letters",

issn = "0378-4274",

publisher = "Elsevier Ireland Ltd",

number = "1",

}

TY - JOUR

T1 - Effects of novel brominated flame retardants on steroidogenesis in primary porcine testicular cells

AU - Mankidy, Rishikesh

AU - Ranjan, Bibhuti

AU - Honaramooz, Ali

AU - Giesy, John P.

PY - 2014/1/3

Y1 - 2014/1/3

N2 - 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. © 2013 Elsevier Ireland Ltd.

AB - 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. © 2013 Elsevier Ireland Ltd.

KW - BFR

KW - In vitro steroidogenesis

KW - NBFR

KW - TBB

KW - TBCO

KW - TBPH

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DO - 10.1016/j.toxlet.2013.10.018

M3 - RGC 21 - Publication in refereed journal

C2 - 24466573

SN - 0378-4274

VL - 224

SP - 141

EP - 146

JO - Toxicology Letters

JF - Toxicology Letters

IS - 1

ER -

Effects of novel brominated flame retardants on steroidogenesis in primary porcine testicular cells

Abstract

Research Keywords

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