Skip to main content

Advertisement

Log in

Effects of Bisphenol A and Fadrozole Exposures on cyp19a1 Expression in the Murray Rainbowfish, Melanotaenia fluviatilis

  • Published:
Archives of Environmental Contamination and Toxicology Aims and scope Submit manuscript

Abstract

Several endocrine-disrupting chemicals (EDCs) have been attributed to the alteration of reproduction in fish through disrupting endogenous sex steroidogenic pathways including aromatisation of androgens to oestrogen by CYP19 aromatase. Here we investigate this hypothesis in adult male and female Melanotaenia fluviatilis by examining the mRNA expression of cyp19a1 isoforms after exposure for ≤96 h to two EDCs with contrasting modes of action: one a weak oestrogen mimic, bisphenol A [BPA (100 or 500 μg/L)], and the other a nonsteroidal aromatase inhibitor, fadrozole [FAD (10 or 50 µg/L)]. The results suggest that BPA did not affect cyp19a1a expression significantly at both concentrations, whereas 50 µg/L of FAD significantly upregulated its expression in ovary. In contrast, BPA exposures increased expression of cyp19a1b in brain of both males and females, whilst FAD had contrasting effects in brain: It increased in males but decreased in females. Similar contrasting responses of cyp19a1b were induced by BPA in gonads: upregulation in ovary and downregulation in testis. FAD did not have a significant effect on gonadal expression of cyp19a1b. Collectively, the results suggest that BPA and FAD can disrupt cyp19a1b activity more readily than can cyp19a1a, albeit with contrasting effects in either a tissue- or sex-specific context that is conceivably consistent with their (BPA and FAD) opposing modes of action. Enhanced spatial and temporal sensitivity of cyp19a1b compared with cyp19a1a suggests that brain sex of fish is more susceptible to disruption by environmental pollutants such as BPA and FAD. Therefore, we propose that the response of cyp19a1b in brain tissue of M. fluviatilis is a more suitable indicator of oestrogenic pollution in the aquatic environment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Alam MA, Bhandari RK, Kobayashi Y, Soyano K, Nakamura M (2006) Induction of sex change within two full moons during breeding season and spawning in grouper. Aquaculture 255:532–535

    Article  Google Scholar 

  • Ankley GT, Kahl MD, Jensen KM, Hornung MW, Korte JJ, Makynen EA et al (2002) Evaluation of the aromatase inhibitor fadrozole in a short-term reproduction assay with the fathead minnow (Pimephales promelas). Toxicol Sci 67:121–130

    Article  CAS  Google Scholar 

  • Balcombe SR, Sheldon F, Capon SJ, Bond NR, Hadwen WL, Marsh N et al (2011) Climate-change threats to native fish in degraded rivers and floodplains of the Murray-Darling Basin, Australia. Mar Freshw Res 62:1099–1114

    Article  Google Scholar 

  • Barney ML, Patil JG, Gunasekera RM, Carter CG (2008) Distinct cytochrome P450 aromatase isoforms in the common carp (Cyprinus carpio): sexual dimorphism and onset of ontogenic expression. Gen Comp Endocrinol 156:499–508

    Article  CAS  Google Scholar 

  • Bhandari RK, Higa M, Nakamura S, Nakamura M (2004) Aromatase inhibitor induces complete sex in protogynous honeycomb grouper, Epinephelus merra. Mol Reprod Dev 67:303–307

    Article  CAS  Google Scholar 

  • Bjerselius R, Lundstedt-Enkel K, Olsen H, Mayer I, Dimberg K (2001) Male goldfish reproductive behaviour and physiology are severely affected by exogenous exposure to 17β-estradiol. Aquat Toxicol 53:139–152

    Article  CAS  Google Scholar 

  • Bolognesi C, Perrone E, Roggieri P, Pampanin D, Sciutto A (2006) Assessment of micronuclei induction in peripheral erythrocytes of fish exposed to xenobiotics under controlled conditions. Aquat Toxicol 78:S93–S98

    Article  CAS  Google Scholar 

  • Bonnefoi HR, Smith IE, Dowsett M, Trunet PF, Houston SJ, Da Luz RJ et al (1996) Therapeutic effects of the aromatase inhibitor fadrozole hydrochloride in advanced breast cancer. Br J Can 73:539–542

    Article  CAS  Google Scholar 

  • Cakmak G, Togan I, Severcan F (2006) 17β-Estradiol induced compositional, structural and functional changes in rainbow trout liver, revealed by FT-IR spectroscopy: a comparative study with nonylphenol. Aquat Toxicol 77:53–56

    Article  CAS  Google Scholar 

  • Callard GV, Tchoudakova AV, Kishida M, Wood E (2001) Differential tissue distribution, developmental programming, estrogen regulation and promoter characteristics of cyp19 genes in teleost fish. J Steroid Biochem Mol Biol 79:305–314

    Article  CAS  Google Scholar 

  • Campbell CG, Sharon E, Borglin SE, Green FB, Grayson A, Wozei E et al (2006) Biologically directed environmental monitoring, fate, and transport of estrogenic endocrine disrupting compounds in water: a review. Chemosphere 65:1265–1280

    Article  CAS  Google Scholar 

  • Carlone DL, Richards JS (1997) Functional interactions, phosphorylation, and levels of 3′,5′-cyclic adenosine monophosphate regulatory element binding protein and steroidogenic factor-1 mediate hormone-regulated and constitutive expression of aromatase in gonadal cells. Mol Endocrinol 11:292–304

    CAS  Google Scholar 

  • Chang CF, Lin BY (1998) Estradiol-17β stimulates aromatase activity and reversible sex change in protandrous black porgy, Acanthopagrus schlegeli. J Exp Zool 280:165–173

    Article  CAS  Google Scholar 

  • Chapin RE, Adams J, Boekelheide K, Gray LE Jr, Hayward SW, Lees PS et al (2008) NTP-CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A. Birth Defects Res B 83:157–395

    Article  CAS  Google Scholar 

  • Chau YM, Crawford PA, Woodson KG, Polish JA, Olson LM, Sadovsky Y (1997) Role of steroidogenic-factor I in basal and 3′,5′-cyclic adenosine monophosphate-mediated regulation of cytochrome P450 side-chain cleavage enzyme in the mouse. Biol Rep 57:765–771

    Article  CAS  Google Scholar 

  • Cheshenko K, Pakdel F, Segner H, Kah O, Eggen RIL (2008) Interference of endocrine disrupting chemicals with aromatase CYP19 expression or activity, and consequences for reproduction of teleost fish. Gen Comp Endocrinol 155:31–62

    Article  CAS  Google Scholar 

  • Devlin RH, Nagahama Y (2002) Sex determination and sex differentiation in fish: an overview of genetic, physiological, and environmental influences. Aquaculture 208:191–364

    Article  CAS  Google Scholar 

  • Fenske M, Segner H (2004) Aromatase modulation alters gonadal differentiation in developing zebrafish (Danio rerio). Aquat Toxicol 67:105–126

    Article  CAS  Google Scholar 

  • Flint S, Markle T, Thompson S, Wallace E (2012) Bisphenol A exposure, effects, and policy: a wildlife perspective. J Environ Manag 104:19–34

    Article  CAS  Google Scholar 

  • Guigen Y, Fostier A, Piferrer F, Chang CF (2010) Ovarian aromatase and estrogens: a pivotal role for gonadal sex differentiation and sex change in fish. Gen Comp Endocrinol 165:352–366

    Article  Google Scholar 

  • Hayashi H, Nishimoto A, Oshima N, Iwamuro S (2007) Expression of the estrogen receptor alpha gene in the anal fin of Japanese medaka, Oryzias latipes, by environmental concentrations of bisphenol A. J Toxicol Sci 32:91–96

    Article  CAS  Google Scholar 

  • Hearn MTW, Gomme PT (2000) Molecular architecture and biorecognition processes of the cystine knot protein superfamily: Part I. The glycoprotein hormones. J Mol Recognit 13:223–278

    Article  CAS  Google Scholar 

  • Kang JH, Asai D, Katayama Y (2007) Bisphenol A in the aquatic environment and its endocrine-disruptive effects on aquatic organisms. Crit Rev Toxicol 37:607–625

    Article  CAS  Google Scholar 

  • Kazeto Y, Ijiri S, Place AR, Zohar Y, Trant JM (2001) The 5′-flanking regions of CYP19A1 and CYP19A2 in zebrafish. Biochem Biophys Res Commun 288:503–508

    Article  CAS  Google Scholar 

  • Kibria G, Haroon Y, Nugegoda D, Rose G (2010) Climate change and chemicals: environmental biology aspects. New Delhi Publishing, New Delhi, p 460

    Google Scholar 

  • Kishida M, Callard GC (2001) Distinct cytochrome P450 aromatase isoforms in zebrafish Danio rerio brain and ovary are differentially programmed and oestrogen regulated during early development. Endocrinology 142:740–750

    CAS  Google Scholar 

  • Komatsu T, Nakamura S, Nakamura M (2006) Masculinization of female golden rabbitfish, Siganus guttatus using an aromatase inhibitor treatment during sex differentiation. Comp Biochem Physiol C 143:402–409

    Google Scholar 

  • Kroon FJ, Munday PL, Westcott DA, Hobbs JPA, Liley NR (2005) Aromatase pathway mediates sex change in each direction. Proc R Soc B 272:1399–1405

    Article  CAS  Google Scholar 

  • Kwon JY, McAndrew BJ, Penman DJ (2002) Treatment with an aromatase inhibitor suppresses high-temperature feminization of genetic male (YY) Nile tilapia. J Fish Biol 60:625–636

    Article  CAS  Google Scholar 

  • Lee YM, Seo JS, Kim IC, Yoon YD, Lee JS (2006) Endocrine disrupting chemicals (bisphenol A, 4-nonylphenol, 4-tert-octylphenol) modulate expression of two distinct cytochrome P450 aromatase genes differently in gender types of the hermaphroditic fish Rivulus marmoratus. Biochem Biophys Res Commun 345:894–903

    Article  CAS  Google Scholar 

  • Li Y, Luh CJ, Burns KA, Arao Y, Jiang Z, Teng CT et al (2013) Endocrine-disrupting chemicals (EDCs): in vitro mechanism of estrogenic activation and differential effects on ER target genes. Environ Health Perspect 121:459–466

    Google Scholar 

  • Liu S, Qin F, Wang H, Wu T, Zhang Y, Zheng Y et al (2012) Effects of 17α-ethinylestradiol and bisphenol A on steroidogenic messenger ribonucleic acid levels in the rare minnow gonads. Aquat Toxicol 122–123:19–27

    Article  Google Scholar 

  • Markey CM, Rubin BS, Soto AM, Sonnenschein C (2002) Endocrine disruptors: from wingspread to environmental developmental biology. J Steroid Biochem Mol Biol 83:235–244

    Article  CAS  Google Scholar 

  • Minghong W, Hai X, Ming Y, Gang X (2011) Effects of chronic bisphenol A exposure on hepatic antioxidant parameters in medaka (Oryzias latipes). Toxicol Environ Chem 93:270–278

    Article  Google Scholar 

  • Muller PY, Janovjak H, Miserez AR, Dobbie Z (2002) Processing of gene expression data generated by quantitative real-time RT-PCR. Biotechniques 32:1372–1379

    CAS  Google Scholar 

  • Oehlmann J, Oetken M, Schulte-Oehlmann U (2008) A critical evaluation of the environmental risk assessment for plasticizers in freshwater environment in Europe, with special emphasis on bisphenol A and endocrine disruption. Environ Res 108:140–149

    Article  CAS  Google Scholar 

  • Page YL, Vosges M, Servili A, Brion F, Kah O (2011) Neuroendocrine effects of endocrine disruptors in teleost fish. J Toxicol Environ Health B 14:370–386

    Article  Google Scholar 

  • Paquette M (2008) Effects of the aromatase inhibitor fadrozole on gene expression in the zebrafish brain. Master’s Thesis. University of Ottawa, Ottowa, Canada, p 96

  • Parker KL, Schimmer BP (1995) Transcriptional regulation of the genes encoding the cytochrome P-450 steroid hydroxylases. Vitam Horm 51:339–369

    Article  CAS  Google Scholar 

  • Patil JG, Gunasekera RM (2008) Tissue and sexually dimorphic expression of ovarian and brain aromatase mRNA in the Japanese Medaka (Oryzias latipes): implications for their preferential roles in ovarian and neural differentiation and development. Gen Comp Endocrinol 158:131–137

    Article  CAS  Google Scholar 

  • Piferrer F, Zanuy S, Carrillo M, Solar II, Devlin RH, Donaldson EM (1994) Brief treatment with an aromatase inhibitor during sex differentiation causes chromosomally female salmon to develop as normal, functional males. J Exp Zool 270:255–262

    Article  Google Scholar 

  • Pollino CA, Georgiades E, Holdway DA (2007) Use of the Australian crimson-spotted rainbowfish (Melanotaenia fluviatilis) as a model test species for investigating the effects of endocrine disruptors. Environ Toxicol Chem 10:2171–2178

    Article  Google Scholar 

  • Ponza P (2006) Molecular markers of ecotoxicological interest in the rainbowfish Melanotaenia fluviatilis. Doctoral Thesis, RMIT University, Melbourne, Victoria, Australia

  • Ruksana S, Pandit NP, Nakamura M (2010) Efficacy of exemestane, a new generation of aromatase inhibitor, on sex differentiation in a gonochoristic fish. Comp Biochem Physiol C 152:69–74

    Google Scholar 

  • Shanthanagouda AH, Patil JG, Nugegoda D (2012) Ontogenic and sexually dimorphic expression of cyp19 isoforms in the rainbowfish, Melanotaenia fluviatilis (Castelnau 1878). Comp Biochem Physiol A 161:250–258

    Article  CAS  Google Scholar 

  • Shanthanagouda AH, Patil JG, Nugegoda (2013a) Effects of exposure to oestrogenic compounds on aromatase gene expression are gender dependent in the rainbowfish, Melanotaenia fluviatilis. Comp Biochem Physiol C 57:162–171

    Google Scholar 

  • Shanthanagouda AH, Nugegoda D, Hassell KL, Patil JG (2013b) Exposure to estrogenic chemicals induces ectopic expression of vtg in the testis of Rainbowfish, Melanotaenia fluviatilis. Bull Environ Contam Toxicol 91:438–443

    Article  CAS  Google Scholar 

  • Staples CA, Dome BP, Klecka GM, Oblock ST, Harris LR (1998) A review of the environmental fate, effects, and exposures of bisphenol A. Chemosphere 36:1249–2179

    Google Scholar 

  • Steele R, Mellor L, Sawyer W, Wasvary J, Browne L (1987) In vitro and in vivo studies demonstrating potent and selective inhibition with the non-steroidal aromatase inhibitor. Steroids 50:147–161

    Article  CAS  Google Scholar 

  • Tompsett AR, Park JW, Zhang X, Jones PD, Newsted JL, Au DWT et al (2009) In situ hybridization to detect spatial gene expression in medaka. Ecotoxicol Environ Saf 72:1257–1264

    Article  CAS  Google Scholar 

  • Uchida D, Yamashita M, Kitano T, Iguchi T (2004) An aromatase inhibitor or high water temperature induce oocyte apoptosis and depletion of P450 aromatase activity in the gonads of genetic female zebrafish during sex-reversal. Comp Biochem Physiol A 137:11–20

    Article  Google Scholar 

  • Villeneuve DL, Knoebl I, Kahl MD, Jensen KM, Hammermeister DE, Greene KJ et al (2006) Relationship between brain and ovary aromatase activity and isoform-specific aromatase mRNA expression in the fathead minnow (Pimephales promelas). Aquat Toxicol 76:353–368

    Article  CAS  Google Scholar 

  • Villeneuve DL, Wang RL, Bencic DC, Biales AD, Martinović D, Lazorchak JM et al (2009) Altered gene expression in the brain and ovaries of zebrafish (Danio rerio) exposed to the aromatase inhibitor fadrozole: microarray analysis and hypothesis generation. Environ Toxicol Chem 28:1767–1782

    Article  CAS  Google Scholar 

  • Wang J, Liu X, Wang H, Wu T, Hu X, Qin F, Wang Z (2010) Expression of two cytochrome P450 aromatase genes is regulated by endocrine disrupting chemicals in rare minnow, Gobiocypris rarus juveniles. Comp Biochem Physiol C 152:313–320

    Google Scholar 

  • Wibbels T, Cowan J, LeBoeuf R (1998) Temperature-dependent sex determination in the red-eared slider turtle, Trachemys scripta. J Exp Zool 281:409–416

    Article  CAS  Google Scholar 

  • Yue W, Brodie A (1997) Mechanisms of the actions of aromatase inhibitors 4-hydroxyandrostenedione, fadrozole, and aminoglutethimide on aromatase in cell culture. J Steroid Biochem Mol Biol 63:317–328

    Article  CAS  Google Scholar 

  • Zhang P, Mellon SH (1997) Multiple orphan nuclear receptors converge to regulate rat P450c17 gene transcription: novel mechanisms for orphan nuclear receptor action. Mol Endocrinol 11:891–904

    Article  CAS  Google Scholar 

Download references

Acknowledgments

A. H. Shanthanagouda was awarded an RMIT University Scholarship (RUIS). The authors thank anonymous reviewers’ suggestions on the manuscript, which helped to improve the quality of the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to A. H. Shanthanagouda or J. G. Patil.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shanthanagouda, A.H., Nugegoda, D. & Patil, J.G. Effects of Bisphenol A and Fadrozole Exposures on cyp19a1 Expression in the Murray Rainbowfish, Melanotaenia fluviatilis . Arch Environ Contam Toxicol 67, 270–280 (2014). https://doi.org/10.1007/s00244-014-0047-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00244-014-0047-1

Keywords

Navigation