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

Abstract

Microcystin-LR (MC-LR) has been detected extensively in the aquatic environment and has the potential to disturb the thyroid endocrine system. However, limited information is available on the effects of subacute MC-LR exposure on fish thyroid hormone (TH) metabolism. In the present study, juvenile zebrafish (Danio rerio) were exposed to MC-LR at environmentally relevant concentrations (0, 1, 5, and 25 μg/L) for 28 days. Whole-body TH content and thyroid follicle histology were used as direct endpoints to assess thyroid disruption. The activities of iodothyronine deiodinases (IDs) and the transcription of selected genes associated with TH synthesis were also investigated to study the underlying mechanisms of endocrine disruption. Exposure of zebrafish to MC-LR significantly increased whole-body thyroxine (T4) content but decreased whole-body triiodothyronine (T3) content. We also observed hypertrophy and hyperplasia of the thyroid follicle epithelial cells, as well as up-regulation of corticotropin-releasing hormone (CRH), thyroid-stimulating hormone (TSH), thyroid peroxidase (TPO), and transthyretin (TTR) genes. The decreases in ID1 and ID2 activities coupled with an increase in ID3 activity were observed in MC-LR treatment groups. These results demonstrate that exposure to MC-LR at environmental concentrations results in the disturbance of TH homeostasis by disrupting the synthesis and conversion of THs.

Persistent Exposure to Environmental Levels of Microcystin-LR Disturbs Cortisol Production via Hypothalamic-Pituitary-Interrenal (HPI) Axis and Subsequently Liver Glucose Metabolism in Adult Male Zebrafish (Danio rerio)

“…It is then not surprising to detect the alterations of relevant HPI-axis genes in the zebrafish brain induced by MC-LR since the brain is the center of neuroendocrinology. Marked up-regulation of the primary neurohormone, CRH, was also reported in zebrafish larvae exposed to 500 µg/L MC-LR for 96 h [37] and in juvenile zebrafish after exposure to 25 µg/L MC-LR for 7, 14, 21 or 28 d [38]. Similar adverse effects on brain CRH contents were observed in studies on other chemicals exposure such as prochloraz [20] and metyrapone [34].…”

A review of reproductive toxicity of microcystins

“…Besides modulating the HPG axis, it has also been previously demonstrated that MCs alter the metabolism of cortisol and thyroid hormone, through activating the hypothalamic-pituitary-adrenal/interrenal (for fish) (HPA/HPI) and hypothalamic-pituitary-thyroid (HPT) axis [130][131][132][133][134][135][136]. As mentioned above, the endocrine system is very complex and affected by many factors, and previous studies have shown that liver damage may not only induce sex hormone changes [127], but also reduce hepatic thyroxine deiodination in animals [137], which in turn causes a decline in peripheral triiodothyronine production [130].…”

Clinical effects of chemical exposures on mitochondrial function

“…In recent years, the deleterious effect of environmental toxins on mitochondrial function has been studied extensively in humans (Eldakroory et al, 2016, Cremonese et al, 2017, Hongsibsong et al, 2017, Sittitoon et al, 2017) and model organisms such as rodents (O’Brien and Wallace, 2004, Suzuki et al, 2008, Butenhoff et al, 2009, Butenhoff et al, 2012), fish (Ge et al, 2017), zebrafish (Bestman et al, 2015, Liu et al, 2015, Jia et al, 2016, Chen et al, 2016, Raftery et al, 2017), Caenorhabditis elegans ( C. elegans ) (Zhou et al, 2013, Liu et al, 2015, Wyatt et al, 2017), and cellular models (Zieminska et al, 2016, D’Mello et al, 2017, Yang et al, 2017). A large number of environmental factors including l-methyl-4phenyl-l, 2, 3, 6-tetra-hydropyridine (MPTP), and pesticides such as rotenone and paraquat are now widely-recognized mitochondrial toxins (Backer and Weinstein, 1980, Harmon and Sanborn, 1982, Nicklas et al, 1987, Youngster et al, 1987) and specifically, neurotoxins.…”