title: The synthetic gestagen Levonorgestrel disrupts sexual development in Xenopus laevis by affecting gene expression of pituitary gonadotropins and gonadal steroidogenic enzymes.
abstract: In the present study, Xenopus laevis tadpoles were chronically exposed to four concentrations of the synthetic gestagen Levonorgestrel (LNG; 10(-11), 10(-10), 10(-9), and 10(-8)M) starting at Nieuwkoop and Faber (NF) stage 48 until completion of metamorphosis. At NF 58 and 66, brain-pituitary and gonad samples were taken for gene expression analyses of gonadotropins and gonadal steroidogenic enzymes. Exposure to 10(-9) and 10(-8)M LNG until NF 58 repressed messenger RNA (mRNA) expression of luteinizing hormone (LH) β in both genders. This decrease was persistent after further treatment until NF 66 in the 10(-8)M LNG treatment. Expression of follicle-stimulating hormone (FSH) β was affected sex-specifically. No effect was present in NF 58 females, whereas LNG at 10(-9) and 10(-8)M significantly increased FSHβ mRNA levels in males. In NF 66 females, 10(-9)M LNG treatment increased FSHβ gene expression, whereas a decrease was observed in NF 66 males exposed to 10(-8)M LNG. In gonads, expression of steroid-5-alpha-reductase was affected sex-specifically with increased mRNA levels in females but repressed levels in males. Gene expression of further gonadal steroidogenic factors was decreased by 10(-8)M LNG in both genders at NF 66. Assessment of gonad gross morphology and histology revealed poorly developed testes in the 10(-8)M LNG treatment. Our results reveal considerable effects of chronic LNG exposure on sexual development of amphibians. The persistent inhibition of LHβ expression concomitant with decreased mRNA levels of gonadal steroidogenic enzymes is suggested to result in the disruption of reproduction in adult amphibians.
authors.affiliation: Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, 12587 Berlin, Germany. claudia.lorenz@igb-berlin.de
authors.forename: Claudia
authors.initials: C
authors.lastname: Lorenz
authors.forename: Valeska
authors.initials: V
authors.lastname: Contardo-Jara
authors.forename: Achim
authors.initials: A
authors.lastname: Trubiroha
authors.forename: Angela
authors.initials: A
authors.lastname: Krüger
authors.forename: Viola
authors.initials: V
authors.lastname: Viehmann
authors.forename: Claudia
authors.initials: C
authors.lastname: Wiegand
authors.forename: Stephan
authors.initials: S
authors.lastname: Pflugmacher
authors.forename: Gunnar
authors.initials: G
authors.lastname: Nützmann
authors.forename: Ilka
authors.initials: I
authors.lastname: Lutz
authors.forename: Werner
authors.initials: W
authors.lastname: Kloas
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics; D000818:Animals; D005260:Female; D037201:Follicle Stimulating Hormone, beta Subunit / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006062:Gonadotropins / Q000235:genetics*; D006066:Gonads / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology / Q000473:pathology; D007814:Larva / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D016912:Levonorgestrel / Q000009:adverse effects*; D037101:Luteinizing Hormone, beta Subunit / Q000235:genetics; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011372:Progestins / Q000009:adverse effects*; D046468:Sexual Development / Q000187:drug effects* / Q000235:genetics; D014982:Xenopus laevis
chemical_list: D037201:Follicle Stimulating Hormone, beta Subunit; D006062:Gonadotropins; D037101:Luteinizing Hormone, beta Subunit; D011372:Progestins; D016912:Levonorgestrel; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C476566:steroid-5alpha-reductase type 1; C476567:steroid-5alpha-reductase type 2