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Reproductive Toxicity in Xenopus tropicalis after Developmental Exposure to Environmental Concentrations of Ethynylestradiol
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
Institutionen för anatomi och fysiologi, SLU.
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: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 91, no 2, 171-178 p.Article in journal (Refereed) Published
Abstract [en]

Reproductive disorders in wildlife and humans have been linked to developmental exposure to endocrine disrupting chemicals. In frog tadpoles, environmental concentrations of ethynylestradiol (EE2) disrupt gonadal differentiation which results in female-biased sex ratios at metamorphosis indicating sex-reversal of genotypic males. It is not known if developmental exposure to estrogens results in reduced reproductive success in amphibians. The objective of this work was to investigate if exposure to environmentally relevant concentrations of EE2 during sex differentiation impairs reproductive organ development, fertility, and sexual behavior in adult frogs. A specific aim was to evaluate if testicular structure and function was affected in males that were not sex-reversed. Xenopus tropicalis tadpoles were exposed until metamorphosis to 6, 60, and 600 pM EE2. Eight months after metamorphosis, reproductive organ morphology and fertility were evaluated. Larval EE2-exposure caused an increased proportion of phenotypic females indicating that sex-reversal of genotypic males is persistent. Sex-reversal was implied at concentrations as low as 6 pM (1.8 ng/l), which is comparable to levels observed in the environment. EE2-exposed males that were not sex-reversed had a significantly reduced fertilization rate compared with control males. Histological evaluation revealed that EE2-exposed males had a reduced amount of spermatozoa in the testis. Among frogs with ovaries there was a significantly higher percentage that lacked oviducts in the group exposed to 600 pM EE2 compared with control females. No effect of EE2 on sexual behavior was noted. The results indicate that reproduction in wild frogs might be impaired by estrogenic environmental pollutants. Similarities between the present effects and those reported in fish, birds and mammals after developmental exposure to estrogens suggest that X. tropicalis is a promising animal model for research on developmental reproductive toxicity.

Place, publisher, year, edition, pages
2009. Vol. 91, no 2, 171-178 p.
Keyword [en]
Amphibians, Endocrine disruption, Estrogen, Sex differentiation, Testicular histology, Sperm quality
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:uu:diva-87137DOI: 10.1016/j.aquatox.2008.06.019ISI: 000263452500010PubMedID: 18692912OAI: oai:DiVA.org:uu-87137DiVA: diva2:1705
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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