Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Effects on differentiation of reproductive organs and sexual behaviour in Japanese quail by excessive embryonic ERα activation

Anna Mattsson A B and Björn Brunström A B C

A Department of Environmental Toxicology, Uppsala University, Norbyvägen 18A, SE-75236 Uppsala, Sweden.

B Centre for Reproductive Biology in Uppsala (CRU).

C Corresponding author. Email: bjorn.brunstrom@ebc.uu.se

Reproduction, Fertility and Development 22(2) 416-425 https://doi.org/10.1071/RD08293
Submitted: 13 December 2008  Accepted: 11 August 2009   Published: 4 January 2010

Abstract

Exposure of Japanese quail (Coturnix japonica) embryos to oestrogenic substances disrupts sexual differentiation of the reproductive tract of both sexes and impairs the copulatory behaviour of the adult male. To examine whether these effects can be induced by selective activation of oestrogen receptor α (ERα), Japanese quail eggs were injected with various doses of the selective ERα agonist 16α-lactone-oestradiol (16α-LE2). The natural oestrogen 17β-oestradiol (E2) was used as a positive control. Both 16α-LE2 and E2 induced formation of an ovary-like cortex in the left testis (ovotestis) and reduced the size of the right testis in male embryos. The asymmetry in testis size remained in sexually mature males. Both substances induced retention and malformation of the Müllerian ducts in embryos of both sexes and malformed oviducts in juveniles. Male copulatory behaviour was suppressed by embryonic exposure to E2 and the highest dose of 16α-LE2. However, the lower dose of 16α-LE2, which markedly affected development of the reproductive organs, was without effects on behaviour. It can therefore not be excluded that the behavioural demasculinisation at the 100-fold higher dose involved cross-activation of oestrogen receptor β (ERβ). In conclusion, our results suggest that oestrogen-induced disruption of reproductive organ development in Japanese quail can be mediated via ERα, whereas the role of ERα in demasculinisation of copulatory behaviour remains to be clarified.

Additional keywords: endocrine disruption, oestrogen receptors, ovotestis, sex differentiation.


Acknowledgements

Bayer Schering Pharma AG (Germany) is acknowledged for kindly providing 16α-LE2. We thank Margareta Mattsson for preparing the histological sections and Johanna Karlsson for performing the image analysis. We also thank Stefan Gunnarsson for advice on the image analysis and Jeanette Axelsson for helpful suggestions on the manuscript. Economic support was given by the Swedish Research Council Formas, and the Swedish Environmental Protection Agency, via the research program ReproSafe.


References

Adkins, E. K. (1979). Effect of embryonic treatment with estradiol or testosterone on sexual differentiation of the quail brain. Critical period and dose-response relationships. Neuroendocrinology 29, 178–185.
CrossRef | PubMed | CAS |

Andrews, J. E. , Smith, C. A. , and Sinclair, A. H. (1997). Sites of estrogen receptor and aromatase expression in the chicken embryo. Gen. Comp. Endocrinol. 108, 182–190.
CrossRef | PubMed | CAS |

Arias-Loza, P. A. , Hu, K. , Dienesch, C. , Mehlich, A. M. , Konig, S. , Jazbutyte, V. , Neyses, L. , Hegele-Hartung, C. , Heinrich Fritzemeier, K. , and Pelzer, T. (2007). Both estrogen receptor subtypes, alpha and beta, attenuate cardiovascular remodelling in aldosterone salt-treated rats. Hypertension 50, 432–438.
CrossRef | PubMed | CAS |

Axelsson, J. , Mattsson, A. , Brunström, B. , and Halldin, K. (2007). Expression of estrogen receptor-alpha and -beta mRNA in the brain of Japanese quail embryos. Dev. Neurobiol. 67, 1742–1750.
CrossRef | PubMed | CAS |

Balthazart, J. , De Clerck, A. , and Foidart, A. (1992). Behavioural demasculinisation of female quail is induced by estrogens: studies with the new aromatase inhibitor, R76713. Horm. Behav. 26, 179–203.
CrossRef | PubMed | CAS |

Berg, C. , Halldin, K. , Fridolfsson, A. K. , Brandt, I. , and Brunström, B. (1999). The avian egg as a test system for endocrine disrupters: effects of diethylstilbestrol and ethynylestradiol on sex organ development. Sci. Total Environ. 233, 57–66.
CrossRef | PubMed | CAS |

Berg, C. , Halldin, K. , and Brunström, B. (2001). Effects of bisphenol A and tetrabromobisphenol A on sex organ development in quail and chicken embryos. Environ. Toxicol. Chem. 20, 2836–2840.
CrossRef | PubMed | CAS |

Blomqvist, A. , Berg, C. , Holm, L. , Brandt, I. , Ridderstråle, Y. , and Brunström, B. (2006). Defective reproductive organ morphology and function in domestic rooster embryonically exposed to o,p′-DDT or ethynylestradiol. Biol. Reprod. 74, 481–486.
CrossRef | PubMed | CAS |

Cheng, K. M. , Hickman, A. R. , and Nichols, C. R. (1989). Role of the proctodeal gland foam of male Japanese quail in natural copulations. Auk 106, 279–285.


Cheskis, B. J. , Greger, J. G. , Nagpal, S. , and Freedman, L. P. (2007). Signalling by estrogens. J. Cell. Physiol. 213, 610–617.
CrossRef | PubMed | CAS |

Elbrecht, A. , and Smith, R. G. (1992). Aromatase enzyme activity and sex determination in chickens. Science 255, 467–470.
CrossRef | PubMed | CAS |

Fridolfsson, A.-K. , and Ellegren, H. (1999). A simple and universal method for molecular sexing of non-ratite birds. J. Avian Biol. 30, 116–121.
CrossRef |

Fry, D. M. , and Toone, C. K. (1981). DDT-induced feminization of gull embryos. Science 213, 922–924.
CrossRef | PubMed | CAS |

Gaido, K. W. , Maness, S. C. , McDonnell, D. P. , Dehal, S. S. , Kupfer, D. , and Safe, S. (2000). Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol. Pharmacol. 58, 852–858.
PubMed | |  CAS |

Gasc, J. M. (1980). Estrogen target cells in gonads of the chicken embryo during sexual differentiation. J. Embryol. Exp. Morphol. 55, 331–342.
PubMed | |  CAS |

Guioli, S. , and Lovell-Badge, R. (2007). PITX2 controls asymmetric gonadal development in both sexes of the chick and can rescue the degeneration of the right ovary. Development 134, 4199–4208.
CrossRef | PubMed | CAS |

Ha, Y. , Tsukada, A. , Saito, N. , and Shimada, K. (2004). Changes in mRNA expression of MMP-2 in the Müllerian duct of chicken embryo. Gen. Comp. Endocrinol. 139, 131–136.
CrossRef | PubMed | CAS |

Halldin, K. , Berg, C. , Brandt, I. , and Brunström, B. (1999). Sexual behaviour in Japanese quail as a test end point for endocrine disruption: effects of in ovo exposure to ethinylestradiol and diethylstilbestrol. Environ. Health Perspect. 107, 861–866.
CrossRef | PubMed | CAS |

Halldin, K. , Holm, L. , Ridderstråle, Y. , and Brunström, B. (2003). Reproductive impairment in Japanese quail (Coturnix japonica) after in ovo exposure to o,p′-DDT. Arch. Toxicol. 77, 116–122.
PubMed | |  CAS |

Halldin, K. , Axelsson, J. , and Brunström, B. (2005). Embryonic co-exposure to methoxychlor and Clophen A50 alters sexual behaviour in adult male quail. Arch. Toxicol. 79, 237–242.
CrossRef | PubMed | CAS |

Harrington, W. R. , Sheng, S. , Barnett, D. H. , Petz, L. N. , Katzenellenbogen, J. A. , and Katzenellenbogen, B. S. (2003). Activities of estrogen receptor alpha- and beta-selective ligands at diverse estrogen-responsive gene sites mediating transactivation or transrepression. Mol. Cell. Endocrinol. 206, 13–22.
CrossRef | PubMed | CAS |

Harris, H. A. (2007). Estrogen receptor-β: recent lessons from in vivo studies. Mol. Endocrinol. 21, 1–13.
CrossRef | PubMed | CAS |

Hill, R. A. , Chow, J. , Fritzemeier, K. , Simpson, E. R. , and Boon, W. C. (2007). Fas/FasL-mediated apoptosis in the arcuate nucleus and medial preoptic area of male ArKO mice is ameliorated by selective estrogen receptor alpha and estrogen receptor beta agonist treatment, respectively. Mol. Cell. Neurosci. 36, 146–157.
CrossRef | PubMed | CAS |

Hillisch, A. , Peters, O. , Kosemund, D. , Muller, G. , Walter, A. , Schneider, B. , Reddersen, G. , Elger, W. , and Fritzemeier, K.-H. (2004). Dissecting physiological roles of estrogen receptor α and β with potent selective ligands from structure-based design. Mol. Endocrinol. 18, 1599–1609.
CrossRef | PubMed | CAS |

Ishimaru, Y. , Komatsu, T. , Kasahara, M. , Katoh-Fukui, Y. , and Ogawa, H. , et al. (2008). Mechanism of asymmetric ovarian development in chick embryos. Development 135, 677–685.
CrossRef | PubMed | CAS |

Kamata, R. , Shiraishi, F. , Izumi, T. , Takahashi, S. , Shimizu, A. , and Shiraishi, H. (2009). Mechanisms of estrogen-induced effects in avian reproduction caused by transovarian application of a xenoestrogen, diethylstilbestrol. Arch. Toxicol. 83, 161–171.
CrossRef | PubMed | CAS |

Lindberg, M. K. , Moverare, S. , Skrtic, S. , Gao, H. , Dahlman-Wright, K. , Gustafsson, J.-Å. , and Ohlsson, C. (2003). Estrogen receptor (ER)-β reduces ERα-regulated gene transcription, supporting a “Ying Yang” relationship between ERα and ERβ in mice. Mol. Endocrinol. 17, 203–208.
CrossRef | PubMed | CAS |

MacLaughlin, D. T. , Hutson, J. M. , and Donahoe, P. K. (1983). Specific estradiol binding in embryonic Müllerian ducts: a potential modulator of regression in the male and female chick. Endocrinology 113, 141–145.
CrossRef | PubMed | CAS |

Mattsson, A. , Mura, E. , Brunström, B. , Panzica, G. , and Halldin, K. (2008a). Selective activation of estrogen receptor alpha in Japanese quail embryos affects reproductive organ differentiation but not the male sexual behaviour or the parvocellular vasotocin system. Gen. Comp. Endocrinol. 159, 150–157.
CrossRef | PubMed | CAS |

Mattsson, A. , Olsson, J. A. , and Brunström, B. (2008b). Selective estrogen receptor α activation disrupts sex organ differentiation and induces expression of vitellogenin II and very low-density apolipoprotein II in Japanese quail embryos. Reproduction 136, 175–186.
CrossRef | PubMed | CAS |

Nettles, K. W. , Sun, J. , Radek, J. T. , Sheng, S. , Rodriguez, A. L. , Katzenellenbogen, J. A. , Katzenellenbogen, B. S. , and Greene, G. L. (2004). Allosteric control of ligand selectivity between estrogen receptors alpha and beta: implications for other nuclear receptors. Mol. Cell 13, 317–327.
CrossRef | PubMed | CAS |

Ohyama, K. , Maki, S. , Sato, K. , and Kato, Y. (2004). In vitro metabolism of [14C]methoxychlor in rat, mouse, Japanese quail and rainbow trout in precision-cut liver slices. Xenobiotica 34, 741–754.
CrossRef | PubMed | CAS |

Panzica, G. C. , Viglietti-Panzica, C. , Mura, E. , Quinn, M. J. , Lavoie, E. , Palanza, P. , and Ottinger, M. A. (2007). Effects of xenoestrogens on the differentiation of behaviourally-relevant neural circuits. Front. Neuroendocrinol. 28, 179–200.
CrossRef | PubMed | CAS |

Romanoff A. L. (1960). ‘The Avian Embryo.’ (The Macmillan Company: New York.)

Routledge, E. J. , White, R. , Parker, M. G. , and Sumpter, J. P. (2000). Differential effects of xenoestrogens on coactivator recruitment by estrogen receptor (ER) alpha and ERbeta. J. Biol. Chem. 275, 35 986–35 993.
CrossRef | CAS |

Scheib, D. (1983). Effects and role of estrogens in avian gonadal differentiation. Differentiation 23(Suppl.), S87–S92.
PubMed |

Schumacher, M. , Sulon, J. , and Balthazart, J. (1988). Changes in serum concentrations of steroids during embryonic and post-hatching development of male and female Japanese quail (Coturnix coturnix japonica). J. Endocrinol. 118, 127–134.
CrossRef | PubMed | CAS |

Shibuya, K. , Mizutani, M. , Sato, K. , Itabashi, M. , and Nunoya, T. (2005). Comparative evaluation of sex reversal effects of natural and synthetic estrogens in sex reversal test using F1 (AWE×WE). J. Poult. Sci. 42, 119–129.
CrossRef | CAS |

Smith, C. A. , and Sinclair, A. H. (2004). Sex determination: insights from the chicken. Bioessays 26, 120–132.
CrossRef | PubMed | CAS |

Smith, C. L. , and O’Malley, B. W. (2004). Co-regulator function: a key to understanding tissue specificity of selective receptor modulators. Endocr. Rev. 25, 45–71.
CrossRef | PubMed | CAS |

Stauffer, S. R. , Coletta, C. J. , Tedesco, R. , Nishiguchi, G. , Carlson, K. , Sun, J. , Katzenellenbogen, B. S. , and Katzenellenbogen, J. A. (2000). Pyrazole ligands: structure-affinity/activity relationships and estrogen receptor-alpha-selective agonists. J. Med. Chem. 43, 4934–4947.
CrossRef | PubMed | CAS |

Viglietti-Panzica, C. , Mura, E. , and Panzica, G. (2007). Effects of early embryonic exposure to genistein on male copulatory behaviour and vasotocin system of Japanese quail. Horm. Behav. 51, 355–363.
CrossRef | PubMed | CAS |

Weiser, M. J. , Foradori, C. D. , and Handa, R. J. (2008). Estrogen receptor beta in the brain: from form to function. Brain Res. Rev. 57, 309–320.
CrossRef | CAS | PubMed |

Woods, J. E. , and Brazzill, D. M. (1981). Plasma 17 beta-estradiol levels in the chick embryo. Gen. Comp. Endocrinol. 44, 37–43.
CrossRef | PubMed | CAS |

Yoshimura, Y. , and Kawai, H. (2002). Structures and androgen receptor localization in the testes and epididymis of Japanese quail hatched from the eggs exposed to diethylstilbestrol. J. Reprod. Dev. 48, 79–85.
CrossRef | CAS |



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