title: Disrupted oogenesis in the frog Xenopus tropicalis after exposure to environmental progestin concentrations.
abstract: Levonorgestrel is a synthetic progesterone commonly used in pharmaceuticals (e.g., in contraceptives). It is found in sewage treatment plant effluents at concentrations up to 30 ng/L and was recently shown to pose a threat to egg laying in fish. Information on the susceptibility of adult amphibians to progestin toxicity is lacking. The present study aimed to 1) characterize progestogenic effects on the full cycle of oogenesis (egg development) in frogs and 2) determine female amphibians' susceptibility to reproductive impacts from progestogenic compounds in the environment. Sexually mature female Xenopus tropicalis   were exposed to levonorgestrel via the surrounding water for 7 days (0, 51, or 307 ng/L) or 28 days (0, 1.3, 18, 160, or 1240 ng/L). Their ovaries were analyzed histologically with respect to frequencies of immature (in early meiotic prophase I), previtellogenic, vitellogenic, mature, and atretic oocytes. The 28-day exposure caused reduced proportions of oocytes at immature, vitellogenic, and mature stages, and increased proportions of previtellogenic oocytes compared with the control. The lowest tested concentration, 1.3 ng/L, increased the proportions of previtellogenic oocytes and reduced the proportions of vitellogenic oocytes, indicating inhibited vitellogenesis. The present study shows that progestin concentrations found in the aquatic environment impaired oogenesis in adult frogs. Our results indicate that progestogenic effects on oocyte development include interrupted germ cell progression into meiosis and inhibited vitellogenesis. Considering the crucial role of oogenesis in female fertility, our results indicate that progestogenic pollutants may pose a threat to reproduction in wild amphibian populations.
authors.affiliation: Department of Environmental Toxicology, Uppsala University, Centre for Reproductive Biology, Uppsala, Sweden. moa.kvarnryd@ebc.uu.se
authors.forename: Moa
authors.initials: M
authors.lastname: Säfholm
authors.forename: Anna
authors.initials: A
authors.lastname: Norder
authors.forename: Jerker
authors.initials: J
authors.lastname: Fick
authors.forename: Cecilia
authors.initials: C
authors.lastname: Berg
mesh_terms: D000818:Animals; D003271:Contraceptive Agents, Female / Q000494:pharmacology* / Q000633:toxicity; D004781:Environmental Exposure; D005260:Female; D016912:Levonorgestrel / Q000494:pharmacology* / Q000633:toxicity; D008540:Meiosis / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects* / Q000473:pathology; D009866:Oogenesis / Q000187:drug effects*; D010053:Ovary / Q000187:drug effects* / Q000473:pathology; D046468:Sexual Development / Q000187:drug effects*; D014818:Vitellogenesis / Q000187:drug effects; D014874:Water Pollutants, Chemical / Q000494:pharmacology / Q000633:toxicity; D014981:Xenopus
chemical_list: D003271:Contraceptive Agents, Female; D014874:Water Pollutants, Chemical; D016912:Levonorgestrel