Adverse effects of BDE-47 on in vivo developmental parameters, thyroid hormones, and expression of hypothalamus-pituitary-thyroid (HPT) axis genes in larvae of the self-fertilizing fish Kryptolebias marmoratus
Introduction
Approximately 150,000 tons of brominated flame retardants (BFRs) have been produced a year since 1975 (WHO, 1997), as these retardants are widely used in plastics, electronics, and textiles to delay or prevent fire damage (OECD, 1994, Alaee and Wenning, 2002). The massive production of BFRs has resulted in growing concerns about their effects on the environment. For example, BFRs at a concentration of 1.21 to 1522 pg/m3 are present in the air of Southern China (Ding et al., 2016), 0.001–0.5 ng/g dry weight BFRs have been documented in Arctic marine sediments (Kelly et al., 2008), and 0.03–0.64 pg/L of BFRs have been measured in the East Greenland sea (Möller et al., 2011). Polybrominated diphenyl ethers (PBDEs) are one of the main components of BFRs that are widely distributed in the aquatic environment and can be transferred via the food web from low-to high-trophic level organisms, thereby threatening the entire aquatic ecosystem (Burreau et al., 2006, Law et al., 2006, Wan et al., 2008). PBDEs are known to cause adverse effects such as neurotoxicity (Costa and Giordano, 2007), immunotoxicity (Martin et al., 2007), and endocrinal toxicity (Legler, 2008). Particularly, PBDEs are responsible in homeostatic imbalance of thyroid hormones (THs) because of their similar chemical structure to THs (Meerts et al., 2000, Miot et al., 2015). Also in mice, follicular cell hyperplasia in thyroid gland was significantly increased in response to BDE209 exposure for 103 weeks (NTP Toxicology Study, 1986) and in U.S. women having thyroid problems, large amount of PBDEs (BDE47, 99, 100, and 153) were observed, implying that PBDEs are responsible for incidence of thyroid disease (Allen et al., 2016).
Of diverse PBDEs congeners, 2,2,4,4-tetrabromodiphenyl ether (BDE-47) is present in large quantities in the environment and thus its endocrine disrupting potency in aquatic organisms is of huge concern (Darnerud et al., 2001, Vos et al., 2003, Petreas et al., 2003). For example, in BDE-47-exposed fathead minnows (Pimephales promelas), fecundity was reduced and sex ratio was biased towards female (Thornton et al., 2016). However, its effect on the thyroid system of fishes is still unclear, despite the fact that several studies have been conducted to understand the endocrine disrupting effect of BDE-47 in fishes.
THs play an important role in regulating energy homeostasis, metamorphosis, growth, immune system, and metabolism (Power et al., 2001, Jugan et al., 2010, Schnitzler et al., 2016). Hypothalamus-pituitary-thyroid (HPT) axis is a thyroid hormone feedback loop that is responsible for TH homeostasis by regulating TH synthesis, transport, maintenance, and circulation (Fekete and Lechan, 2014). Abnormal function of THs causes malformation, developmental impairments, and cancer in vertebrates (Goldey et al., 1995, Soto and Sonnenschein, 2010, Gilbert et al., 2012).
The mangrove killifish Kryptolebias marmoratus is the only selfing fish (Harrington, 1961, Atz, 1965) and is considered to be a good model species for ecotoxicological and carcinogenesis studies because of its genetic homogeneity, easy maintenance, small size, and strong tolerance to environmental challenges (Lee et al., 2008, Rhee and Lee, 2014). In addition, the K. marmoratus genome has been sequenced (Rhee et al., 2017). K. marmoratus is susceptible to develop thyroid tumors in response to the methylating agent N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) (Park et al., 1993). Thus, we hypothesized that K. marmoratus would be a good model species in which to elucidate the adverse effects of BDE-47 and examined the toxicity of BDE-47 to K. marmoratus larvae by monitoring in vivo endpoints of body length, weight, and hatching time. Furthermore, we measured transcript levels of genes involved in TH homeostasis and the HPT-axis along with thyroid hormone levels. In this paper, we provide insights into potent impact of BDE-47 on early development and endocrine disruption in K. marmoratus.
Section snippets
Fish rearing conditions
K. marmoratus were maintained at the aquarium facility of Sungkyunkwan University (Suwon, South Korea) and reared in accordance with the Animal Welfare Ethical Committee of the Sungkyunkwan University. Briefly, the fish were maintained in automatically controlled conditions at 25 °C with a light/dark ratio of 12L:12D and artificial seawater (ASW; TetraMarine Salt Pro, Tetra™, Cincinnati, OH, USA; 5.71 ± 0.19 mg O2/L) adjusted to 15 practical salinity units (psu). The automated water-changing
Developmental toxicity
Mortality was not observed in K. marmoratus embryos and larvae in response to exposure to 0.1, 1, 10, 100, or 1000 μg/L BDE-47 (data not shown). In BDE-47-exposed embryos, dorsal malformation was observed (Fig. S1), while the hatching time and body lengths and weights of hatchlings were slightly decreased without significance (Table 1). However, in the case of BDE-47-exposed K. marmoratus larvae, body length and weight were significantly decreased (P < 0.05) compared to the control group (
Discussion
In K. marmoratus larvae, BDE-47 exposure led to a decrease in body length and weight. However, in K. marmoratus embryos, BDE-47 had no significant effect on the hatching time and body length and weight. The difference in toxicity of BDE-47 to embryos and larvae may be because of the protective role of the chorion. For example, in the zebrafish Danio rerio and the Japanese medaka Oryzias latipes, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and benzene were much more toxic to the dechorionated
Acknowledgements
This work was supported by a grant from the Development of Techniques for Assessment and Management of Hazardous Chemicals in the Marine Environment of the Ministry of Oceans and Fisheries, Korea funded to Jae-Seong Lee.
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2021, Environmental PollutionCitation Excerpt :This result is akin to a prior study that maternal exposure to low doses of commercial PBDE mixture DE-71 (containing PBDE-47) during pregnancy increased the serum T3 levels in adult female rat offspring (Blake et al., 2011). Studies on fishes and birds have also shown a significant increase in whole-body T3 levels in response to PBDEs or their hydroxylated metabolites during development (Guigueno and Fernie, 2017; Kang et al., 2017; Zhao et al., 2016). However, opposite results were observed after exposure to PBDEs during the developmental period in some other rodent researches (Bondy et al., 2013; He et al., 2011; Sarkar and Singh, 2018).