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Xenopus tropicalis as a Test System for Developmental and Reproductive Toxicity
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.
2009 (English)In: Journal of Toxicology and Environmental Health, ISSN 1528-7394, E-ISSN 1087-2620, Vol. 72, no 3-4, 219-225 p.Article in journal (Refereed) Published
Abstract [en]

The usefulness of Xenopus tropicalis as a model species to investigate endocrine disruption and developmental reproductive toxicity was assessed. In our test system tadpoles were exposed to test substances from shortly after hatching until metamorphosis, including the period of gonadal differentiation. Effects on the sex hormone and thyroid hormone axes were evidenced as skewed sex ratios, malformations of reproductive organs, altered cytochrome (CYP19) (aromatase) activity, and gene expression in gonads and brain, as well as changed thyroid histology and time to metamorphosis. Reproductive toxicity was evaluated at sexual maturity. Male-to-female sex reversal was implied at concentrations as low as 6 pM (1.8 ng/L) ethynylestradiol (EE2), which is comparable to EE2 levels observed in the environment. EE2-exposed males that were not sex reversed had significantly reduced fertility and a reduced amount of spermatozoa in testes compared with control males. This indicates that reproduction in wild frogs might be impaired by estrogenic environmental pollutants. Aromatase activity in brain and testes of adult frogs was not affected by larval EE2 exposure. Preliminary results indicate that exposure to the environmentally relevant pharmaceutical clotrimazole modulated aromatase activity in brain and gonads during sex differentiation, which warrants further investigation. The susceptibility to estrogen-induced sex reversal of X. tropicalis was comparable to that of other frog species and fish. Similarities between the reproductive effects in X. tropicalis and those reported in fish, birds, and mammals after developmental exposure to estrogens make X. tropicalis promising model for research on endocrine disruption and developmental reproductive toxicity.

Place, publisher, year, edition, pages
2009. Vol. 72, no 3-4, 219-225 p.
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-87138DOI: 10.1080/15287390802539079ISI: 000263013000011OAI: oai:DiVA.org:uu-87138DiVA: diva2:1704
Available from: 2008-09-15 Created: 2008-09-15 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Endocrine Disruption in Amphibians: Developmental Effects of Ethynylestradiol and Clotrimazole on the Reproductive System
Open this publication in new window or tab >>Endocrine Disruption in Amphibians: Developmental Effects of Ethynylestradiol and Clotrimazole on the Reproductive System
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Amphibian populations are declining world-wide and one of the suggested reasons is environmental pollutants. Studies of long-term effects on the reproductive system in frogs following larval exposure to environmental pollutants are scarce. It is therefore important to develop methods to study developmental reproductive toxicity in amphibians. In this thesis the usefulness of Xenopus tropicalis (the West African clawed frog) as a model species for a test system was investigated. Effects on the reproductive system after larval exposure to the pharmaceuticals ethynylestradiol (EE2) and clotrimazole were evaluated. The susceptibility to EE2 exposure was compared between the model species and a wild species, the European common frog (Rana temporaria). Larval exposure to EE2 caused female-biased sex ratios in both examined frog species, indicating male-to-female sex-reversal. In adult Xenopus tropicalis, male frogs that were not sex-reversed had reduced fertility and decreased amount of mature spermatozoa in the seminiferous tubules. The proportion of frogs with ovaries but lacking oviducts increased with increasing EE2-concentrations. A female frog without oviducts is sterile. The development of ovaries in sex-reversed male frogs was implied to be similar to control females. The combination of a reduced number of males, due to sex-reversal, and impaired fertility could have severe effects on frog populations. Larval exposure to clotrimazole modulated aromatase activity in gonads and brain in Xenopus tropicalis. Brain aromatase activity was decreased at the time for gonadal differentiation and gonadal aromatase activity was increased at metamorphosis. The findings in this thesis indicate that reproduction in wild frogs might be impaired by estrogenic compounds in the environment. The results combined with the short generation time supports the use of Xenopus tropicalis as a model species when evaluating long term effects of endocrine disruptors on the reproductive system in amphibians.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 57 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 545
Keyword
Test system, Xenopus tropicalis, Rana temporaria, sex ratio, sex differentiation, fertility, aromatase, ovary, testis, oviduct
National Category
Biological Sciences
Identifiers
urn:nbn:se:uu:diva-9209 (URN)978-91-554-7260-3 (ISBN)
Public defence
2008-09-26, Lindahlsalen, Evolutionsbiologisk centrum (EBC), Norbyvägen 18A, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2008-09-05 Created: 2008-09-05 Last updated: 2013-09-06Bibliographically approved

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