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Selective estrogen receptor alpha activation disrupts sex organ differentiation and induces expression of vitellogenin II and very low-density apolipoprotein II in Japanese quail embryos
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
2008 (English)In: Reproduction, ISSN 1470-1626, E-ISSN 1476-3990, Vol. 136, no 2, 175-186 p.Article in journal (Refereed) Published
Abstract [en]

The Japanese quail (Coturnix japonica) is a widely used model species for studying the roles of steroid hormones in avian sex differentiation. The aim of the present study was to elucidate the significance of estrogen receptors alpha and beta (ER alpha and ER beta) in normal sex differentiation of the reproductive organs in the Japanese quail and in xenoestrogen-induced disruption of reproductive organ differentiation. Real-time PCR indicated that ER alpha (ESR1) mRNA is expressed in both right and left gonads and Mullerian ducts (MDs) in both sexes during early morphological differentiation. ER beta (ESR2) transcripts were also detected in gonads and MDs, but at very low levels. Both receptor subtypes were expressed in the liver and may therefore mediate the expression of estrogen-regulated egg-yolk proteins. Aromatase mRNA was expressed at much higher levels in female than male gonads as early as embryonic day 5, indicating early sex differences in estrogen synthesis. Treatment with the ER alpha-selective agonist propyl pyrazole triol showed that frequently reported xenoestrogen effects, such as ovotestis formation, abnormal MD development, and hepatic expression of egg-yolk proteins, were induced by selective activation of ER alpha. Taken together, our results suggest that activation of ER alpha is crucial for estrogen-dependent sex differentiation of the reproductive organs and that ER alpha mediates xenoestrogen-induced toxicity during reproductive development in birds.

Place, publisher, year, edition, pages
2008. Vol. 136, no 2, 175-186 p.
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:uu:diva-97339DOI: 10.1530/REP-08-0100ISI: 000258671500005OAI: oai:DiVA.org:uu-97339DiVA: diva2:172231
Available from: 2008-05-22 Created: 2008-05-22 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Roles of ERα and ERβ in Normal and Disrupted Sex Differentiation in Japanese Quail
Open this publication in new window or tab >>Roles of ERα and ERβ in Normal and Disrupted Sex Differentiation in Japanese Quail
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Exposure to xenoestrogens during development has been shown to impair sexual differentiation in various species. The major aim of this thesis was to elucidate the respective roles of the two estrogen receptors ERα and ERβ in normal and disrupted differentiation of sex organs and copulatory behavior in the Japanese quail (Coturnix japonica). The expression of ERα mRNA was much stronger than that of ERβ mRNA in the gonads and Müllerian ducts (embryonic oviducts) in early embryos. By contrast, ERβ seemed to be predominantly expressed in regions of the embryonic brain that are associated with male sexual behavior. Embryos were exposed to the selective ERα agonists propyl-pyrazole-triol (PPT) and 16α-lactone-estradiol (16α-LE2). The estrogens 17β-estradiol (E2) and 17α-ethynylestradiol (EE2), which activate both ERα and ERβ, were used as positive controls. All substances impaired reproductive organ differentiation. The effects observed included oviductal malformations in females and partial development of oviducts in males. All substances also induced testis feminization (ovotestis) in male embryos. The male copulatory behavior was severely impaired by the positive controls but was unaffected by PPT and 16α-LE2 at doses that disrupted sex organ differentiation. A higher dose of 16α-LE2 significantly suppressed the behavior. However, it is possible that this effect was caused by cross-activation of ERβ. The substances also induced hepatic expression of mRNA encoding the egg-yolk proteins vitellogenin II and very low-density apolipoprotein II, which are commonly used as indicators of estrogen exposure. In conclusion, the results suggest that ERα is important for female reproductive organ differentiation. Excess activation of ERα by xenoestrogens impairs differentiation in both females and males and induces hepatic expression of egg-yolk proteins. The results also indicate that ERα alone cannot mediate demasculinization of male copulatory behavior in quail, although further studies are needed to test this hypothesis.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 68 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 445
Keyword
Toxicology, sex differentiation, estrogen receptor, sexual behavior, endocrine disruption, Japanese quail, Toxikologi
Identifiers
urn:nbn:se:uu:diva-8921 (URN)978-91-554-7232-0 (ISBN)
Public defence
2008-06-12, Lindahlsalen, Evolutionsbiologiskt centrum (EBC), Norbyvägen 18A, Uppsala, 13:15 (English)
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Available from: 2008-05-22 Created: 2008-05-22 Last updated: 2010-01-07Bibliographically approved

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Mattsson, AnnaBrunström, Björn

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