Effects of Triclocarban on Intact Immature Male Rat: Augmentation of Androgen Action

Dulęba, Antoni J.; Ahmed, Mohamed; Sun, Meng; Gao, Allen C.; Villanueva, Jesus A.; Conley, Alan J; Turgeon, Judith L; Benirschke, Kurt; Gee, Nancy A.; Chen, Jiangang; Green, Peter G.; Lasley, Bill L.

doi:10.1177/1933719110382581

Cited by 34 publications

(26 citation statements)

References 36 publications

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“…Enhancement was typically in the range of 20% to 40%, a finding confirmed in subsequent studies (34,35,63). In vivo studies using castrated male rats found that exposure to TCC and testosterone together significantly increased the weights of several male sex accessory organs and reproductive tract tissues relative to exposure to testosterone alone (34,35). Our work using zebrafish embryos confirms that TCC has enhancing effects on estrogen-stimulated gene transcription and provides a demonstration that TCC can enhance expression of a well-established, physiologically relevant estrogen target gene in vivo.…”

Section: Discussionsupporting

confidence: 65%

“…One micromolar of TCC by itself had little agonist activity toward any of these receptors but enhanced hormone-dependent induction of ER-and AR-dependent transcription of reporter constructs in cell-based assays. Enhancement was typically in the range of 20% to 40%, a finding confirmed in subsequent studies (34,35,63). In vivo studies using castrated male rats found that exposure to TCC and testosterone together significantly increased the weights of several male sex accessory organs and reproductive tract tissues relative to exposure to testosterone alone (34,35).…”

Section: Discussionsupporting

confidence: 61%

“…TCC by itself exhibits little or no agonist activity, but it increases hormonestimulated transcription of androgen receptor (AR) and ER reporter constructs in mammalian tissue culture cells by up to 30% (33). In vivo, TCC strongly amplifies effects of testosterone on male sex organs in castrated male rats (34,35). In snails, TCC can stimulate an increase in embryo production, a response that has been used previously in that system to assay for xenoestrogens (36).…”

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confidence: 99%

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Effects of bisphenol A and triclocarban on brain-specific expression of aromatase in early zebrafish embryos

Chung

Genco

Megrelis

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

134

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Estrogen regulates numerous developmental and physiological processes. Most effects are mediated by estrogen receptors (ERs), which function as ligand-regulated transcription factors. Estrogen also regulates the activity of GPR30, a membrane-associated G protein-coupled receptor. Many different types of environmental contaminants can activate ERs; some can bind GPR30 as well. There is growing concern that exposure to some of these compounds, termed xenoestrogens, is interfering with the behavior and reproductive potential of numerous wildlife species, as well as affecting human health. Here, we investigated how two common, environmentally pervasive chemicals affect the in vivo expression of a known estrogen target gene in the brain of developing zebrafish embryos, aromatase AroB, which converts androgens to estrogens. We confirm that, like estrogen, the well-studied xenoestrogen bisphenol A (BPA, a plastics monomer), induces strong brain-specific overexpression of aromatase. Experiments using ER- and GPR30-selective modulators argue that this induction is largely through nuclear ERs. BPA induces dramatic overexpression of AroB RNA in the same subregions of the developing brain as estrogen. The antibacterial triclocarban (TCC) by itself stimulates AroB expression only slightly, but TCC strongly enhances the overexpression of AroB that is induced by exogenous estrogen. Thus, both BPA and TCC have the potential to elevate levels of aromatase and, thereby, levels of endogenous estrogens in the developing brain. In contrast to estrogen, BPA-induced AroB overexpression was suppressed by TCC. These results indicate that exposures to combinations of certain hormonally active pollutants can have outcomes that are not easily predicted from their individual effects.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionsupporting

confidence: 61%

mentioning

confidence: 99%

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Effects of bisphenol A and triclocarban on brain-specific expression of aromatase in early zebrafish embryos

Chung

Genco

Megrelis

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

134

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“…Interaction with endogenous hormones to potentially affect development of sex organs and interfere with reproduction has also been reported [9–12]. In cells, exposure to TCC at micromolar concentrations has been shown to enhance estradiol or testosterone dependent activation of estrogen and androgen responsive genes [9].…”

Section: Introductionmentioning

confidence: 99%

Maternal exposure to an environmentally relevant dose of triclocarban results in perinatal exposure and potential alterations in offspring development in the mouse model

et al. 2017

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Triclocarban (TCC) is among the top 10 most commonly detected wastewater contaminants in both concentration and frequency. Its presence in water, as well as its propensity to bioaccumulate, has raised numerous questions about potential endocrine and developmental effects. Here, we investigated whether exposure to an environmentally relevant concentration of TCC could result in transfer from mother to offspring in CD-1 mice during gestation and lactation using accelerator mass spectrometry (AMS). 14 C-TCC (100 nM) was administered to dams through drinking water up to gestation day 18, or from birth to post-natal day 10. AMS was used to quantify 14 C-concentrations in offspring and dams after exposure. We demonstrated that TCC does effectively transfer from mother to offspring, both trans-placentally and via lactation. TCC-related compounds were detected in the tissues of offspring with significantly higher concentrations in the brain, heart and fat. In addition to transfer from mother to offspring, exposed offspring were heavier in weight than unexposed controls demonstrating an 11% and 8.5% increase in body weight for females and males, respectively. Quantitative real-time polymerase chain reaction (qPCR) was used to examine changes in gene expression in liver and adipose tissue in exposed offspring. qPCR suggested alterations in genes involved in lipid metabolism in exposed female offspring, which was consistent with the observed increased fat pad weights and hepatic triglycerides. This study represents the first report to quantify the transfer of an environmentally relevant concentration of TCC from mother to offspring in the mouse model and evaluate bio-distribution after exposure using AMS. Our findings suggest that early-life exposure to TCC may interfere with lipid metabolism and could have implications for human health.

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“…This stemmed from TCC's apparent ability to enhance hormone-dependent induction of estrogen receptor (ER)-and androgen receptor (AR)dependent gene expression in vitro [13][14][15][16]. In vivo studies in rats have supported the in vitro evidence that TCC augments, but does not directly elicit, androgen action [14,17]. Similarly, in a previous study with fathead minnow, TCC (10 mg/L) enhanced 17b trenbolone (TRB)-induced formation of nuptial tubercles (a male secondary sex characteristic) in females exposed to mixtures of the 2 chemicals for 21 d [18].…”

Section: Introductionmentioning

confidence: 99%

Effects of the antimicrobial contaminant triclocarban, and co-exposure with the androgen 17β-trenbolone, on reproductive function and ovarian transcriptome of the fathead minnow (Pimephales promelas)

Villeneuve

Jensen

Cavallin

et al. 2016

Environmental Toxicology and Chemistry

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Triclocarban (TCC) is an antimicrobial agent routinely detected in surface waters that has been hypothesized to interact with the vertebrate endocrine system. The present study examined the effects of TCC alone and in combination with the model endocrine disruptor 17β-trenbolone (TRB) on fish reproductive function. Adult Pimephales promelas were continuously exposed to either 1 µg TCC/L or 5 µg TCC/L, to 0.5 µg TRB/L, or to a mixture (MIX) of 5 µg TCC/L and 0.5 µg TRB/L for 22 d, and a variety of reproductive and endocrine-related endpoints were examined. Cumulative fecundity was significantly reduced in fathead minnows exposed to TRB, MIX, or 5 µg TCC/L. Exposure to 1 µg TCC/L had no effect on reproduction. In general, both TRB and MIX treatments caused similar physiological effects, evoking significant reductions in female plasma vitellogenin, estradiol, and testosterone, and significant increases in male plasma estradiol. Based on analysis of the ovarian transcriptome, there were potential pathway impacts that were common to both TRB- and TCC-containing treatment groups. In most cases, however, those pathways were more plausibly linked to differences in reproductive status than to androgen-specific functions. Overall, TCC was reproductively toxic to fish at concentrations at or near those that have been measured in surface water. There was little evidence that TCC elicits reproductive toxicity through a specific mode of endocrine or reproductive action, nor that it could augment the androgenic effects of TRB. Nonetheless, the relatively small margin of safety between some measured environmental concentrations and effect concentrations suggests that concern is warranted. Environ Toxicol Chem 2017;36:231-242. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

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Effects of Triclocarban on Intact Immature Male Rat: Augmentation of Androgen Action

Cited by 34 publications

References 36 publications

Effects of bisphenol A and triclocarban on brain-specific expression of aromatase in early zebrafish embryos

Effects of bisphenol A and triclocarban on brain-specific expression of aromatase in early zebrafish embryos

Maternal exposure to an environmentally relevant dose of triclocarban results in perinatal exposure and potential alterations in offspring development in the mouse model

Effects of the antimicrobial contaminant triclocarban, and co-exposure with the androgen 17β-trenbolone, on reproductive function and ovarian transcriptome of the fathead minnow (Pimephales promelas)

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