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Chronic Exposure to Two Gestagens Differentially Alters Morphology and Gene Expression in Silurana tropicalis

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Abstract

Gestagens are active ingredients in human and veterinary drugs with progestogenic activity. Two gestagens—progesterone (P4), and the synthetic P4 analogue, melengestrol acetate (MGA)—are approved for use in beef cattle agriculture in North America. Both P4 and MGA have been measured in surface water receiving runoff from animal agricultural operations. This project aimed to assess the morphometric and molecular consequences of chronic exposures to P4, MGA, and their mixture during Western clawed frog metamorphosis. Chronic exposure (from embryo to metamorphosis) to MGA (1.7 µg/L) or P4 + MGA (0.22 µg/L P4 + 1.5 µg/L MGA) caused a considerable dysregulation of metamorphic timing, as evidenced by an inhibition of growth, narrower head, and lack of forelimb emergence in all animals. Molecular analysis revealed that chronic exposure to the mixture induced an additive upregulation of neurosteroid-related (GABAA receptor subunit α6 (gabra6) and steroid 5-alpha reductase 1 (srd5α1) gene expression in brain tissue. Chronic P4 exposure (0.26 µg/L P4) induced a significant upregulation of the expression hypothalamic–pituitary–gonadal (HPG)-related genes (ipgr, erα) in the gonadal mesonephros complex (GMC). Our data suggest that exposure to P4, MGA, and their mixture induces multiple endocrine responses and adverse effects in larval Western clawed frogs. This study helps to better our understanding of the consequences of chronic gestagen exposure and suggests that the implications and risk of high gestagen use in beef cattle feeding operations may extend to the aquatic environment.

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Acknowledgements

The authors wish to acknowledge Sarah Wallace (Royal Military College of Canada, ON (RMCC), Chrissy Emerton (RMCC), and Tash-Lynn Colson (Queen’s University, ON), and Meghan Hinds (RMCC) for their contributions with animal care, sampling, and molecular analyses.

Funding

This research project was funded by the support of a Discovery Grant of the Natural Sciences and Engineering Research Council of Canada [NSERC-DG-418576-2102] and the Canada Research Chair [CRC-950-230442] to VSL.

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  1. Institut national de la recherche scientifique (INRS) - Centre Eau Terre Environnement, 490 rue de la Couronne, Québec City, QC, G1K 9A9, Canada

    Paisley Thomson & Valerie S. Langlois

  2. Department of Chemical Engineering, McGill University, 3610 University St, Montreal, QC, H3A 0C5, Canada

    Marco Pineda & Viviane Yargeau

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  1. Paisley Thomson
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  2. Marco Pineda
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  4. Valerie S. Langlois
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Correspondence to Valerie S. Langlois.

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Thomson, P., Pineda, M., Yargeau, V. et al. Chronic Exposure to Two Gestagens Differentially Alters Morphology and Gene Expression in Silurana tropicalis. Arch Environ Contam Toxicol 80, 745–759 (2021). https://doi.org/10.1007/s00244-021-00831-5

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