The synthetic gestagen Levonorgestrel disrupts sexual development in Xenopus laevis by affecting gene expression of pituitary gonadotropins and gonadal steroidogenic enzymes

International audienceIn the present study, Xenopus laevis tadpoles were chronically exposed to four concentrations of the synthetic gestagen Levonorgestrel (LNG; 10211, 10210, 1029, and 1028M) 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 1029 and 1028M LNG until NF 58 repressed messenger RNA (mRNA) expression of luteinizing hormone (LH) b in both genders. This decrease waspersistent after further treatment until NF 66 in the 1028M LNG treatment. Expression of follicle-stimulating hormone (FSH) b was affected sex-specifically. No effect was present in NF 58 females, whereas LNG at 1029 and 1028M significantly increased FSHb mRNA levels in males. In NF 66 females, 1029M LNG treatment increased FSHb gene expression, whereas a decrease was observed in NF 66 males exposed to 1028M 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 1028M LNG in both genders at NF 66.Assessment of gonad gross morphology and histology revealed poorly developed testes in the 1028M LNG treatment. Our results reveal considerable effects of chronic LNG exposure on sexual development of amphibians. The persistent inhibition of LHb expression concomitant with decreased mRNA levels of gonadal steroidogenic enzymes is suggested to result in the disruption of reproduction in adult amphibians