Transcriptomic change as evidence for cadmium-induced endocrine disruption in marine fish model of medaka, Oryzias javanicus Youn-Jung Kim Nayoung Lee Seonock Woo Jae-Chun Ryu Seungshic Yum Email author Original Paper First Online: 07 January 2017 Received: 31 March 2016 Accepted: 29 July 2016 DOI :
10.1007/s13273-016-0045-7
Cite this article as: Kim, YJ., Lee, N., Woo, S. et al. Mol. Cell. Toxicol. (2016) 12: 409. doi:10.1007/s13273-016-0045-7
Abstract We evaluated cadmium (Cd)-induced acute toxicity in Oryzias javanicus (marine medaka or Javanese ricefish) and gathered transcriptomic evidence for the Cd-induced endocrine-disrupting effect. The median lethal concentrations for the fish were determined to be 44.25 and 27.80 mg/L after exposure to Cd in seawater for 24 and 48 h, respectively, and 2.84, 1.61, and 1.20 mg/L after exposure in freshwater for 24, 48, and 72 h, respectively. The differences in the bioavailability and activity of free Cd2+ caused by the salt concentration in seawater could explain these dramatic differences in the toxicity of Cd between marine and fresh water system. The genes differentially expressed in O. javanicus liver tissue after exposure to 280 μg/L CdCl2 for 48 h were profiled with a customized marine medaka cDNA microarray (HazChem Fish Array). We identified 204 differentially expressed genes; the expression of 66 genes was upregulated and that of 138 genes was downregulated (P <0.05). The total 31 genes were commonly expressed in fish exposed to Cd and two references of environmental disruptor (bisphenol A, or 17β-estradiol). These genes were used to predict the changes that occur in metabolic pathways and processes in response to Cd exposure. The database for annotation, visualization and integrated discovery (DAVID) was used for functional analysis for the differentially expressed genes. Significant changes were predicted in the steroid hormone and estrogen stimulus response, vitellogenin expression, sterol and cholesterol metabolic processes, lipid transport activity, defense response, innate immune response, and metal ion binding activity. These results extend our knowledge of the toxicity of Cd at the molecular level and indicate that Cd exposure causes endocrine disruption in aquatic organisms.
Keywords Transcriptomic responses Metabolic changes prediction Oryzias javanicus Cadmium Bisphenol A 17β-Estradiol Endocrine disrupting chemical These authors contributed equally to this work.
References 1.
Iavicoli, I., Fontana, L. & Bergamaschi, A. The effects of metals as endocrine disruptors.
J Toxicol Environ Health B Crit Rev
12 :206–223 (2009).
CrossRef PubMed Google Scholar 2.
Piasek, M. & Laskey, J. W. Acute cadmium exposure and ovarian steroidogenesis in cycling and pregnant rats.
Reprod Toxicol
8 :495–507 (1994).
CrossRef PubMed Google Scholar 3.
Lafuente, A., Cano, P. & Esquifino, A. Are cadmium effects on plasma gonadotropins, prolactin, ACTH, GH and TSH levels, dose-dependent?
Biometals
16 :243–250 (2003).
CrossRef PubMed Google Scholar 4.
Zeng, X., Lin, T., Zhou, Y. & Kong, Q. Alterations of serum hormone levels in male workers occupationally exposed to cadmium.
J Toxicol Environ Health A
65 : 513–521 (2002).
CrossRef PubMed Google Scholar 5.
Jurasovic, J.
et al . Semen quality and reproductive endocrine function with regard to blood cadmium in Croatian male subjects.
Biometals
17 :735–743 (2004).
CrossRef PubMed Google Scholar 6.
Garcia-Morales, P.
et al . Effect of cadmium on estrogen receptor levels and estrogen-induced responses in human breast cancer cells.
J Biol Chem
269 :16896–16901 (1994).
PubMed Google Scholar 7.
Inoue, K. & Takei, Y. Diverse adaptability in Oryzias species to high environmental salinity.
Zoolog Sci
19 : 727–734 (2002).
CrossRef PubMed Google Scholar 8.
Inoue, K. & Takei, Y. Asian medaka fishes offer new models for studying mechanisms of seawater adaptation.
Comp Biochem Physiol B Biochem Mol Biol
136 : 635–645 (2003).
CrossRef PubMed Google Scholar 9.
Woo, S.
et al . Heavy metal-induced differential gene expression of metallothionein in Javanese medaka, Oryzias javanicus.
Mar Biotechnol (NY)
8 :654–662 (2006).
CrossRef Google Scholar 10.
Woo, S.
et al . Effects of heavy metals on antioxidants and stress-responsive gene expression in Javanese medaka (
Oryzias javanicus ).
Comp Biochem Physiol C Toxicol Pharmacol
149 :289–299 (2009).
CrossRef PubMed Google Scholar 11.
Woo, S. & Yum, S. Transcriptional response of marine medaka (
Oryzias javanicus ) on exposure to toxaphene.
Comp Biochem Physiol C Toxicol Pharmacol
153 :355–361 (2011).
CrossRef PubMed Google Scholar 12.
Woo, S., Yum, S., Kim, D. W. & Park, H. S. Transcripts level responses in a marine medaka (Oryzias javanicus) exposed to organophosphorus pesticide.
Comp Biochem Physiol C Toxicol Pharmacol
149 :427–432 (2009).
CrossRef PubMed Google Scholar 13.
Woo, S., Denis, V. & Yum, S. Transcriptional changes caused by bisphenol A in Oryzias javanicus, a fish species highly adaptable to environmental salinity.
Mar Drugs
12 :983–998 (2014).
CrossRef PubMed PubMedCentral Google Scholar 14.
Woo, S.
et al . Expreßsion profiling of liver in Java medaka fish exposed to 17ß-estradiol.
Mol Cell Toxicol
7 :271–281 (2011).
CrossRef Google Scholar 15.
Woo, S., Won, H., Lee, A. & Yum, S. Oxidative streßs and gene expression in diverse tissues of Oryzias javanicus exposed to 17ß-estradiol.
Mol Cell Toxicol
8 :263–269 (2012).
CrossRef Google Scholar 16.
Yum, S., Jo, Y. J. & Woo, S. Metabolic changes in marine medaka fish (
Oryzias javanicus ) in response to acute 4-nonlyphenol toxicity.
BioChip J
9 :322–331 (2015).
CrossRef Google Scholar 17.
James, M. O. Steroid catabolism in marine and freshwater fish.
J Steroid Biochem Mol Biol
127 :167–175 (2011).
CrossRef PubMed Google Scholar 18.
Kishida, M., McLellan, M., Miranda, J. A. & Callard, G. V. Estrogen and xenoestrogens upregulate the brain aromatase isoform (P450aromB) and perturb markers of early development in zebrafish (Danio rerio).
Comp Biochem Physiol B Biochem Mol Biol
129 :261–268 (2001).
CrossRef PubMed Google Scholar 19.
Wright, D. A. & Welbourn, P. M. Cadmium in the aquatic environment: a review of ecological, physiological, and toxicological effects on biota.
Environ Rev
2 :187–214 (1994).
CrossRef Google Scholar 20.
Lee, A.
et al . Changes in gene expression profile due to acute toxicity of toxaphene in the marine medaka.
Mol Cell Toxicol
9 :121–128 (2013).
CrossRef Google Scholar 21.
Henson, M. C. & Chedrese, P. J. Endocrine disruption by cadmium, a common environmental toxicant with paradoxical effects on reproduction.
Exp Biol Med (Maywood)
229 :383–392 (2004).
Google Scholar 22.
Huang da, W., Sherman, B. T. & Lempicki, R. A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.
Nat Protoc
4 :44–57 (2009).
CrossRef Google Scholar 23.
Huang da, W., Sherman, B. T. & Lempicki, R. A. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists.
Nucleic Acids Res
37 :1–13 (2009).
CrossRef Google Scholar 24.
Kashiwada, S.
et al . Fish test for endocrine-disruption and estimation of water quality of Japanese rivers.
Water Res
36 :2161–2166 (2002).
CrossRef PubMed Google Scholar 25.
Pettersson, K. & Gustafsson, J. A. Role of estrogen receptor beta in estrogen action.
Annu Rev Physiol
63 : 165–192 (2001).
CrossRef PubMed Google Scholar 26.
Meyer, C., Schmid, R., Scriba, P. C. & Wehling, M. Purification and partial sequencing of high-affinity progesterone-binding site (s) from porcine liver membranes.
Eur J Biochem
239 :726–731 (1996).
CrossRef PubMed Google Scholar 27.
Losel, R. M., Besong, D., Peluso, J. J. & Wehling, M. Progesterone receptor membrane component 1-many tasks for a versatile protein.
Steroids
73 :929–934 (2008).
CrossRef PubMed Google Scholar 28.
Stan, S.
et al . Apo A-IV: an update on regulation and physiologic functions.
Biochim Biophys Acta
1631 : 177–187 (2003).
CrossRef PubMed Google Scholar 29.
Rohe, H. J., Ahmed, I. S., Twist, K. E. & Craven, R. J. PGRMC1 (progesterone receptor membrane component 1): a targetable protein with multiple functions in steroid signaling, P450 activation and drug binding.
Pharmacol Ther
121 :14–19 (2009).
CrossRef PubMed Google Scholar 30.
Mallory, J. C.
et al . Dap1p, a heme-binding protein that regulates the cytochrome P450 protein Erg11p/Cyp51p in Saccharomyces cerevisiae.
Mol Cell Biol
25 :1669–1679 (2005).
CrossRef PubMed PubMedCentral Google Scholar © The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Science+Business Media Dordrecht 2016
Authors and Affiliations Youn-Jung Kim Nayoung Lee Seonock Woo Jae-Chun Ryu Seungshic Yum Email author 1. Department of Marine Sciences Incheon National University Incheon Republic of Korea 2. South Sea Environment Research Center Korea Institute of Ocean Science and Technology (KIOST) Geoje Republic of Korea 3. Faculty of Marine Environmental Science University of Science and Technology (UST) Geoje Republic of Korea 4. Center for Environment, Health and Welfare Research Korea Institute of Science and Technology (KIST) Seoul Republic of Korea