title: Xenopus tropicalis as a test system for developmental and reproductive toxicity.
abstract: 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.
authors.affiliation: Department of Environmental Toxicology, Uppsala University, Centre for Reproductive Biology in Uppsala (CRU), Norbyvägen 18 A, Uppsala, Sweden. Cecilia.Berg@ebc.uu.se
authors.forename: Cecilia
authors.initials: C
authors.lastname: Berg
authors.forename: Irina
authors.initials: I
authors.lastname: Gyllenhammar
authors.forename: Moa
authors.initials: M
authors.lastname: Kvarnryd
mesh_terms: D000818:Animals; D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D003022:Clotrimazole / Q000494:pharmacology; D012734:Disorders of Sex Development; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000633:toxicity*; D004997:Ethinyl Estradiol / Q000633:toxicity*; D005260:Female; D005298:Fertility / Q000187:drug effects; D007814:Larva / Q000187:drug effects / Q000254:growth & development; D008297:Male; D023421:Models, Animal; D012098:Reproduction / Q000187:drug effects*; D012733:Sex Differentiation / Q000187:drug effects; D012744:Sex Ratio; D013076:Sperm Count; D013094:Spermatozoa / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D018675:Toxicity Tests / Q000379:methods*; D014981:Xenopus / Q000502:physiology*
chemical_list: D047072:Aromatase Inhibitors; D004967:Estrogens; D004997:Ethinyl Estradiol; D001141:Aromatase; D003022:Clotrimazole