J Hazard Mater 2024 Nov 13;480:136493. doi: 10.1016/j.jhazmat.2024.136493.

Effects of mifepristone, a model compound with anti-progestogenic activity, on the reproduction of African clawed frog (Xenopus laevis).

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This is the first study on how a substance with anti-progestogenic activity affects amphibian reproduction. Mifepristone, a synthetic anti-progestin used in abortion pills, was chosen as model compound. African clawed frog (Xenopus laevis) females were exposed to four mifepristone concentrations (0.7, 9, 120, and 1380 ng∙L-1) for 30 days. A control group was also included. Egg-laying during the experiment was significantly less at the highest concentration. At the experiment's end, mifepristone-exposed and control females were randomly mated with sexually mature males. Breeding rate for females exposed to 1380 ng∙L-1 mifepristone was only 50 %. Histology revealed no significant changes in gonads, thyroid, or liver. Females exposed to 1380 ng∙L-1 mifepristone had lower estradiol levels in plasma, lower mRNA expression of lh and fsh in brain-pituitary complex, and p450scc in ovaries. In liver, mRNA level of npr was significantly increased in females exposed to 120 ng∙L-1 mifepristone. mRNA expression of mpr, erβ, dio2, and dio3 were upregulated in animals exposed to 9 ng∙L-1 and 120 ng∙L-1 mifepristone, whereas vtg expression was significantly downregulated in females exposed to 1380 ng∙L-1 mifepristone. All these findings show that exposure to compounds with anti-progestogenic activity affects the hypothalamus-pituitary-gonad axis and decreases reproductive success.

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Genes referenced: cyp11a1 dio2 dio3 nptxr