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Antagonistic Mixture Effects of Levonorgestrel and Ethinylestradiol on Androgen Receptor mRNA Expression during Sex Differentiation.
(English)Article in journal (Refereed) Submitted
National Category
Natural Sciences
URN: urn:nbn:se:uu:diva-210988OAI: oai:DiVA.org:uu-210988DiVA: diva2:665005
Available from: 2013-11-18 Created: 2013-11-18 Last updated: 2014-02-10
In thesis
1. Developmental and Reproductive Toxicity of Progestagens in the Xenopus (Silurana) tropicalis Test System
Open this publication in new window or tab >>Developmental and Reproductive Toxicity of Progestagens in the Xenopus (Silurana) tropicalis Test System
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Progestagenic compounds are emerging contaminants found in surface and ground water around the world. Information on the effects and potency of progestagens is needed in order to understand the environmental risks posed by these compounds. Using the Xenopus (Silurana) tropicalis test system, developmental and reproductive toxicity after exposure to selected progestagens were determined. Larval exposure to levonorgestrel (LNG) severely impaired oviduct and ovary development causing sterility. No effects on testicular development, spermcount or male fertility were observed. Hepatic mRNA expression of the androgen receptor was increased in the females indicating that the receptor is involved in LNG-induced developmental reproductive toxicity. Exposure of adult females to LNG, norethindrone (NET) or progesterone (P) increased the proportions of previtellogenic oocytes and reduced the proportions of vitellogenic oocytes compared with the controls, indicating an inhibited vitellogenesis. The effects on oocyte development were ascertained at environmentally relevant concentrations of LNG, NET and P (1.3, 1 and 10 ng/L respectively). Since unintentional co-exposure of progestagens and ethinylestradiol (EE2) occurs in wildlife and also in human infants, data on mixture effects of combined exposures to these hormones during development are needed. Co-exposure during development showed antagonistic effects of EE2 and LNG. EE2 caused a female biased sex ratio which showed a tendency to be antagonized by LNG. Moreover, the hepatic AR induction by LNG was counteracted by co-exposure to EE2. In conclusion, the results show that female amphibians are susceptible to reproductive toxicity of progestagens after developmental exposure as well as after adult exposure during the breeding period. The differentiating Müllerianduct and ovary, and the egg development are sensitive targets for progestagens. Finally, the findings reported in this thesis show that environmental progestagens impairs reproductive function in amphibians and may present a threat to reproduction in wild populations.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. 51 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1099
Xenopus tropicalis, sex organ differentiation, oogenesis, fertility, ovary, oviduct, progestagens
National Category
Natural Sciences
Research subject
Biology with specialization in Environmental Toxicology
urn:nbn:se:uu:diva-210990 (URN)978-91-554-8812-3 (ISBN)
Public defence
2014-02-14, Auditorium Minus, Museum Gustavianum, Akademigatan 3, Uppsala, 09:00 (English)
Available from: 2014-01-23 Created: 2013-11-18 Last updated: 2014-02-10Bibliographically approved

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