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Early life progestin exposure causes arrested oocyte development, oviductal agenesis and sterility in adult Xenopus tropicalis frogs
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
2011 (English)In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 103, no 1-2, 18-24 p.Article in journal (Refereed) Published
Abstract [en]

Levonorgestrel (LNG) is a commonly used pharmaceutical progestin found in the environment. Information on the long-term toxicity of progestins following early life exposure is scant. We investigated the effects of developmental LNG exposure on sex differentiation, reproductive organ development and fertility in the model frog Xenopus tropicalis. Tadpoles were exposed to 0, 0.06 or 0.5 nM LNG via the water from hatching until metamorphosis. At metamorphosis effects on gonadal differentiation were evaluated using a subsample of frogs. Remaining animals were held unexposed for nine months, at which time reproductive organ structure, function and fertility were determined. LNG exposure severely impaired oviduct and ovary development and fertility. All adult females in the 0.5 nM group (n = 10) completely lacked oviducts. They also displayed a significantly larger fraction of immature oocytes, arrested in meiotic prophase, than control females. Upon mating with unexposed males, only one of 11 LNG-exposed females laid eggs, whereas all control females did. No effects on testicular development, sperm count or male fertility were observed. At metamorphosis, no effects on sex ratio or gonadal histology were evident. The effects on ovarian and oviductal development were detected at adult age but not at metamorphosis, emphasising the importance of investigating the long-term consequences of developmental exposure. This is the first developmental reproductive toxicity study of a progestin in an aquatic vertebrate. Considering that several progestins are present in contaminated surface waters, further investigation into the sensitivity of frogs to progestins is warranted to understand the risk such compounds may pose to wild frog populations.

Place, publisher, year, edition, pages
2011. Vol. 103, no 1-2, 18-24 p.
Keyword [en]
Endocrine disruption, Developmental reproductive toxicity, Levonorgestrel, Oogenesis, Oviduct, Sex differentiation
National Category
Biological Sciences
Research subject
Ecotoxicology
Identifiers
URN: urn:nbn:se:uu:diva-153282DOI: 10.1016/j.aquatox.2011.02.003ISI: 000290502000003PubMedID: 21392492OAI: oai:DiVA.org:uu-153282DiVA: diva2:415977
Available from: 2011-05-10 Created: 2011-05-10 Last updated: 2017-12-11Bibliographically approved
In thesis
1. The Frog as a Model for Studies on Reproductive Toxicity of Progestagenic Environmental Pollutants
Open this publication in new window or tab >>The Frog as a Model for Studies on Reproductive Toxicity of Progestagenic Environmental Pollutants
2011 (English)Licentiate thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Uppsala: Institutionen för organismbiologi, 2011
National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-154029 (URN)
Available from: 2011-07-19 Created: 2011-05-24 Last updated: 2011-07-19Bibliographically approved
2. 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.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1099
Keyword
Xenopus tropicalis, sex organ differentiation, oogenesis, fertility, ovary, oviduct, progestagens
National Category
Natural Sciences
Research subject
Biology with specialization in Environmental Toxicology
Identifiers
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)
Opponent
Supervisors
Available from: 2014-01-23 Created: 2013-11-18 Last updated: 2014-02-10Bibliographically approved

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