Developmental exposure to pentachlorophenol affects the expression of thyroid hormone receptor β1 and synapsin I in brain, resulting in thyroid function vulnerability in rats

Abstract

Pentachlorophenol (PCP), a component of biocides and a contaminant in diverse tissue samples from humans from various geographic areas, disrupts regulatory effects of thyroid hormones. Here we examined the effects of developmental exposure of rats to PCP on various aspects of brain development, male reproductive function, and adrenal function, all of which are under thyroid hormones regulation. PCP was administered to dams and their offspring via drinking water (6.6 mg l(-1)) during gestation and lactation. Tissue samples were obtained from dams, 3-week-old weanling pups, and 12-week-old pups. Gene expressions of thyroid hormone receptor beta1 and synapsin I, factors that promote brain growth, was increased in the cerebral cortex of PCP-treated weanling females, whereas plasma concentrations of total thyroxine were decreased in dams and weanling pups, and plasma thyroid-stimulating hormone concentrations were higher in PCP-treated weanling males. PCP caused a decrease in plasma corticosterone concentrations in 12-week-old female rats, but not in male rats or weanling females. PCP-treated male pups had significantly increased testis weight at 12 week of age. No overt signs of toxicity were noted throughout this study. Our results show that PCP exposure during development causes thyroid function vulnerability, testicular hypertrophy in adults, and aberrations of brain gene expression.

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

“…Although the reason for the sex difference is unclear, a previous study also reported a similar result, in which significant increased TT3 levels and unaltered TT3 levels were observed in PCP‐Na–treated female and male rats, respectively . The significant decrease in T3 observed in our study is consistent with previous studies , and the observed decrease in T3, at least in part, can be attributed to the thyroid hormone metabolism‐disrupting properties of PCP. Indeed, this observation corresponds with the PCP‐induced downregulation of dio2 and upregulation of sult1st5 observed in the liver of male fish.…”

Thyroid endocrine system disruption by pentachlorophenol: An in vitro and in vivo assay

“…PCP decreased the plasma T4 levels in rats (BruckerDavis, 1998;Kawaguchi et al, 2008). Decreased T4 levels are frequently observed in mammals, amphibian and fish models exposed to TH endocrine disruptors, e.g., PBDEs (Tomy et al, 2004;Ellis-Hutchings et al, 2006;Lema et al, 2008;Yu et al, 2010), PCBs (Donahue et al, 2004;Martin and Klaassen, 2010;Schnitzler et al, 2011), and perchlorates (Mukhi and Patino, 2007;Opitz et al, 2009;Schmidt et al, 2012).…”

“…For example, in Xenopus laevis, PCP was shown to have T3-antagonist activity by in vitro and in vivo assays (Sugiyama et al, 2005). Developmental exposure to PCP in rats caused lowered total T4 concentrations in plasma (Kawaguchi et al, 2008). In humans, a negative association between maternal plasma PCP levels and cord plasma free T4 (fT4) concentrations in neonates was reported (Dallaire et al, 2009).…”

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

“…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).…”