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

Michal Pech; Christoph Steinbach; Martin Kocour; Ilona Prokopová; Marie Šandová; Adam Bořík; Ilka Lutz; Hana Kocour Kroupová

doi:10.1016/j.aquatox.2023.106694

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

Aquat Toxicol. 2023 Oct:263:106694. doi: 10.1016/j.aquatox.2023.106694. Epub 2023 Sep 10.

Authors

Michal Pech¹, Christoph Steinbach², Martin Kocour², Ilona Prokopová², Marie Šandová², Adam Bořík², Ilka Lutz³, Hana Kocour Kroupová²

Affiliations

¹ Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Research Institute of Fish Culture and Hydrobiology, University of South Bohemia in České Budějovice, Zátiší 728/II, Vodňany, 389 25, Czech Republic. Electronic address: pechm@frov.jcu.cz.
² Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Research Institute of Fish Culture and Hydrobiology, University of South Bohemia in České Budějovice, Zátiší 728/II, Vodňany, 389 25, Czech Republic.
³ Leibniz-Institute of Freshwater Ecology and Inland Fisheries (IGB), Müggelseedamm 310, Berlin 12587, Federal Republic of Germany.

PMID: 37716317
DOI: 10.1016/j.aquatox.2023.106694

Abstract

The objective of this study was to assess the effects of a model substance with anti-progestogenic activity on development of African clawed frog (Xenopus laevis) from tadpole to juvenile stage. Mifepristone, a synthetic progesterone receptor-blocking steroid hormone used in medicine as an abortifacient, was chosen as a model compound with anti-progestogenic activity. In the experiment, African clawed frog tadpoles were exposed to mifepristone at three concentrations (2, 21, and 215 ng L^-1). A control group was exposed to dimethyl sulfoxide (DMSO; 0.001 %). The experiment started when tadpoles reached stages 47-48 according to Nieuwkoop and Faber (NF; 1994) and continued until stage NF 66, when metamorphosis was complete. Exposure to mifepristone had no significant effect on the rate of tadpole development, occurrence of morphological anomalies, weight, body length, or sex ratio. Mortality was within an acceptable range of 0-3.6 % throughout the test and did not differ among the groups. Histopathological examination of the gonads and thyroid gland revealed no significant changes. Therefore, we can conclude that mifepristone had no negative effect on development of the African clawed frog up to juvenile stage. Nevertheless, at the highest tested mifepristone concentration (215 ng L^-1), gene expression analysis revealed up-regulation of mRNA expression of nuclear progesterone receptor (npr), membrane progesterone receptor (mpr), estrogen receptor beta (esrβ), and luteinizing hormone (lh) in the brain-pituitary complex of exposed frogs at stage NF 66. Higher mRNA expression of npr was also found in frogs exposed to 22 ng L^-1 mifepristone compared to the solvent control. These findings confirmed the anti-progestogenic activity of mifepristone in frogs because the up-regulation of progesterone receptors occurs if progesterone availability in the body is reduced. All the observed changes in combination may have negative consequences for reproduction and reproductive behavior later in life.

Keywords: Brain; Gonads; Luteinizing hormone; Progesterone; Tadpoles; Thyroid.

MeSH terms

Animals
Larva
Metamorphosis, Biological
Mifepristone / toxicity
Progestins* / pharmacology
RNA, Messenger
Receptors, Progesterone / genetics
Water Pollutants, Chemical* / toxicity
Xenopus laevis

Substances

Progestins
Mifepristone
Receptors, Progesterone
Water Pollutants, Chemical
RNA, Messenger