Chronic exposure to pentachlorophenol alters thyroid hormones and thyroid hormone pathway mRNAs in zebrafish

Abstract

Pentachlorophenol (PCP) is frequently detected in the aquatic environment and has been implicated as an endocrine disruptor in fish. In the present study, 4-month-old zebrafish (Danio rerio) were exposed to 1 of 4 concentrations of PCP (0.1, 1, 9, and 27 µg/L) for 70 d. The effects of PCP exposure on plasma thyroid hormone levels, and the expression levels of selected genes, were measured in the brain and liver. The PCP exposure at 27 µg/L resulted in elevated plasma thyroxine concentrations in male and female zebrafish and depressed 3, 5, 3'-triiodothyronine concentrations in males only. In both sexes, PCP exposure resulted in decreased messenger RNA (mRNA) expression levels of thyroid-stimulating hormone β-subunit (tshβ) and thyroid hormone receptor β (trβ) in the brain, as well as increased liver levels of uridine diphosphoglucuronosyl transferase (ugt1ab) and decreased deiodinase 1 (dio1). The authors also identified several sex-specific effects of PCP exposure, including changes in mRNA levels for deiodinase 2 (dio2), cytosolic sulfotransferase (sult1 st5), and transthyretin (ttr) genes in the liver. Environmental PCP exposure also caused an increased malformation rate in offspring that received maternal exposure to PCP. The present study demonstrates that chronic exposure to environmental levels of PCP alters plasma thyroid hormone levels, as well as the expression of genes associated with thyroid hormone signaling and metabolism in the hypothalamic-pituitary-thyroid (HPT) axis and liver, resulting in abnormal zebrafish development.

Progesterone and norgestrel alter transcriptional expression of genes along the hypothalamic–pituitary–thyroid axis in zebrafish embryos-larvae

“…This is in agreement with a previous study which has also demonstrated that P4 could inhibit the expression of Dio2 mRNA in the ovary of female zebrafish (Zucchi et al, 2013). Previous studies had provided evidence that the down-regulation of Dio1 and Dio2 mRNAs could reduce the conversion of T4 to T3 (Liu et al, 2011a;Yu et al, 2014). However, transcripts of Dio1 and Dio2 genes in response to P4 and NGT were generally low, and consequently may cause minor effects on the production of thyroid hormones in the present study.…”

Relative developmental toxicities of pentachloroanisole and pentachlorophenol in a zebrafish model (Danio rerio)

“…Previous reports indicated possible thyroid disrupting effects on animals after exposure to PCP by regulation of HPT axis-related genes expression Guo and Zhou, 2013;Hughes et al, 1985;Jekat et al, 1994;Yu et al, 2014), but this is the first report showing similar thyroid disrupting effects after PCA exposure. Our results show that PCA can also affect gene expression related to thyroid hormone regulation similar to PCP.…”

“…PCP was found to disrupt thyroid functions of the rat offspring (Kawaguchi et al, 2008) and zebrafish Yu et al, 2014) by altering hypothalamus-pituitary-thyroid (HPT) axis related gene expressions and thyroid homone levels. Sub-lethal effects of PCP on the development of zebrafish embryo have been reported (Duan et al, 2008).…”

Subacute Microcystin-LR Exposure Alters the Metabolism of Thyroid Hormones in Juvenile Zebrafish (Danio Rerio)

“…Transthyretin (TTR) has been reported as a TH-binding and transport protein in fish [ 24 ], which can non-covalently bind most THs in the blood and regulate free TH levels [ 47 , 48 ]. It plays a key role in maintaining the peripheral storage of TH and regulates the supply of TH to different target tissues [ 49 , 50 ]. The differences in the results of TH and free TH levels may be attributable to the changes in the mRNA expression of TTR induced by MC-LR.…”