Short-Term Exposure Effects of the Environmental Endocrine Disruptor Benzo(a)Pyrene on Thyroid Axis Function in Zebrafish

Abstract

Benzo(a)Pyrene (BaP) is one of the most widespread polycyclic aromatic hydrocarbons (PAHs) with endocrine disrupting properties and carcinogenic effects. In the present study, we tested the effect of BaP on thyroid development and function, using zebrafish as a model system. Zebrafish embryos were treated with 50 nM BaP from 2.5 to 72 h post fertilization (hpf) and compared to 1.2% DMSO controls. The expression profiles of markers of thyroid primordium specification, thyroid hormone (TH) synthesis, hypothalamus-pituitary-thyroid (HPT) axis, TH transport and metabolism, and TH action were analyzed in pools of treated and control embryos at different developmental stages. BaP treatment did not affect early markers of thyroid differentiation but resulted in a significant decrease of markers of TH synthesis (tg and nis) likely secondary to defective expression of the central stimulatory hormones of thyroid axis (trh, tshba) and of TH metabolism (dio2). Consequently, immunofluorescence of BaP treated larvae showed a low number of follicles immunoreactive to T4. In conclusion, our results revealed that the short-term exposure to BaP significantly affects thyroid function in zebrafish, but the primary toxic effects would be exerted at the hypothalamic-pituitary level thus creating a model of central hypothyroidism.

Effects of Benzo (a) Pyrene and 2,2′,4,4′-Tetrabromodiphenyl Ether Exposure on the Thyroid Gland in Rats by Attenuated Total Reflection Fourier-Transform Infrared Spectroscopy

“…B­[ a ]P exposure significantly decreased the circulatory concentrations of T3 and T4 and increased the circulatory concentrations of thyroid-stimulating hormone in the treated rats and fish. , Another study suggested that the primary toxic effects of short-term exposure to B­[ a ]P in zebrafish was compromised hypothalamic-pituitary function, which would then hamper the adequate functional maturation of thyroid follicles and TH synthesis. The main toxic effect of short-term exposure to B­[ a ]P in zebrafish is impaired hypothalamic-pituitary function, which prevents the full functional maturation of thyroid follicles and hormone synthesis . BDE-47 exposure in vivo can alter the secretion of thyroid hormones and change the status of thyroid gland in rats and fish. − Elevated serum T3 levels after exposure to BDE-47 in rats are consistent with an epidemiological study showing that plasma concentrations of BDE-47 in adults are positively correlated with serum T3 levels. , A systematic review suggests that exposure to PBDEs and the interaction of PBDEs (or their metabolites) with the TH transport system or thyroid receptors may lead to increased T4 metabolism and excretion .…”

“…The main toxic effect of short-term exposure to B[ a ]P in zebrafish is impaired hypothalamic-pituitary function, which prevents the full functional maturation of thyroid follicles and hormone synthesis. 31 BDE-47 exposure in vivo can alter the secretion of thyroid hormones and change the status of thyroid gland in rats and fish. 9 − 11 Elevated serum T3 levels after exposure to BDE-47 in rats are consistent with an epidemiological study showing that plasma concentrations of BDE-47 in adults are positively correlated with serum T3 levels.…”

Mining Potential Drug Targets for Osteoporosis Based on CeRNA Network

“…Related studies had shown that polycyclic aromatic hydrocarbons were associated with cancer, immunosuppression, decreased resistance to viral and bacterial infections, and decreased endocrine function. 52 , 53 , 54 , 55 BaP could also inhibit osteoclast formation and bone resorption by binding to aryl hydrocarbon receptor (Ahr), which related to the inhibition of RANKL signal pathway. 56 , 57 Moreover, studies demonstrated BaP inhibited TGF‐β1/SMAD4 and TGF‐β1/ERK/AKT signaling pathways by activating Ahr, thus inhibiting the osteogenic differentiation of BMSC.…”

“…Benzo[a]pyrene (BaP) is a typical polycyclic aromatic hydrocarbon, which usually exists in cigarette smoke and smog. Related studies had shown that polycyclic aromatic hydrocarbons were associated with cancer, immunosuppression, decreased resistance to viral and bacterial infections, and decreased endocrine function 52–55 . BaP could also inhibit osteoclast formation and bone resorption by binding to aryl hydrocarbon receptor (Ahr), which related to the inhibition of RANKL signal pathway 56,57 .…”

Short-Term Exposure to Benzo(a)Pyrene Causes Disruption of GnRH Network in Zebrafish Embryos

“…The working doses of BaP (5 and 50 nM) were used and administered as previously reported by Gao et al and our group [ 19 , 33 ]. For each experiment, pools of 100 embryos were raised in glass petri dish (diam.…”