Elsevier

Chemosphere

Volume 176, June 2017, Pages 39-46
Chemosphere

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

https://doi.org/10.1016/j.chemosphere.2017.02.081Get rights and content

Highlights

  • Transcript levels of genes involved in TH homeostasis and HPT axis-related genes were measured.

  • The expression of thyroid hormone metabolism-related genes (e.g. deiodinases, UGT1ab) and HPT axis-related genes was up-regulated.

  • There were significant changes in TH levels (P < 0.05) in response to BDE-47 exposure.

Abstract

2,2′,4,4′-tetrabromodiphenylether (BDE-47) is known to have the potential to disrupt the thyroid endocrine system in fishes due to its structural similarity to the thyroid hormones triiodothyronine (T3) and thyroxine (T4). However, the effects of BDE-47 on thyroid function in fishes remain unclear. In this study, abnormal development (e.g. deformity, hemorrhaging) and an imbalance in thyroid hormone (TH) homeostasis was shown in the early developmental stages of the mangrove killifish Kryptolebias marmoratus in response to BDE-47 exposure. To examine the thyroid endocrinal effect of BDE-47 exposure in mangrove killifish K. marmoratus larvae, transcript levels of genes involved in TH homeostasis and hypothalamus-pituitary-thyroid (HPT) axis-related genes were measured. The expression of thyroid hormone metabolism-related genes (e.g. deiodinases, UGT1ab) and HPT axis-related genes was up-regulated and there were significant changes in TH levels (P < 0.05) in response to BDE-47 exposure. This study provides insights into the regulation of TH homeostasis at the transcriptional level and provides a better understanding on the potential impacts of BDE-47 on the thyroid endocrine system of fishes.

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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