Citation:

Skolness, S., C. Blanksma, J. Cavallin, J. Churchill, E. Durhan, K. Jensen, R. Johnson, M. Kahl, L. Makynen, Dan Villeneuve, AND G. Ankley. Propiconazole inhibits steroidogenesis and reproduction in the fathead minnow (Pimephales promelas). TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 132(2):284-297, (2013).

Impact/Purpose:

This study assessed effects of the conazole-fungicide propiconazole on endocrine function and reproductive success of the fathead minnow, using an experimental approach based on previously defined adverse outcome pathways (AOPs) for chemicals that inhibit steroidogenesis in fish. Conazoles are a class of chemicals that inhibit cytochrome P450 (CYP) 14-alpha-demethylase (CYP51), an enzyme key to fungal cell wall development. In vertebrates, several other CYP enzymes also are targets for conazoles, potentially disrupting processes such as xenobiotic metabolism and sex steroid synthesis. Propiconazole is of particular interest because it is a current-use pesticide, due to undergo reregistration by the US Environmental Protection Agency (USEPA) in the near future, and also is one of about 60 chemicals being tested in the USEPA Tier 1 screening program for endocrine disrupting chemicals. Fathead minnows (Pimephales promelas) were exposed to 0, 5, 50, 500, 1000 µg propiconazole/L in a 21-d study that evaluated apical reproductive endpoints (fecundity, fertility, hatch), as well as bioconcentration of the chemical in the fish. In addition, cholesterol, triglycerides, vitellogenin (VTG), and sex steroid (testosterone [T], 17â-estradiol [E2]) concentrations were determined in the plasma of the fish, and changes in expression of several gonadal and hepatic genes involved to steroid synthesis, and cholesterol and xenobiotic metabolism were measured. Plasma E2 and VTG concentrations in females were significantly reduced by exposure to propiconazole, and egg production was decreased in a concentration-dependent fashion in the 500 and 1000 µg/L treatment groups. These effects coincided with inhibition of E2 synthesis by propiconazole by ovary explants in in vitro experiments. We also observed a compensatory response in females exposed to propiconazole, manifested as increased gonad weight and up-regulation of genes coding for key steriodogenic proteins, including CYP19 (aromatase), CYP17 (hydroxylase/lyase), CYP11A (cholesterol side-chain-cleavage), and steroid acute regulatory protein. Effects on endocrine function in males were less pronounced than in females, although there was a significant increase in relative testis weight. Results of these studies provide important data specific to the potential endocrine and reproductive toxicity of propiconazole in fish and, more generally, to the further derivation/validation of AOPs for the reproductive effects of steroid synthesis inhibitors in fish.

Description:

This study assessed effects of the conazole-fungicide propiconazole on endocrine function and reproductive success of the fathead minnow, using an experimental approach based on previously defined adverse outcome pathways (AOPs) for chemicals that inhibit steroidogenesis in fish. Conazoles are a class of chemicals that inhibit cytochrome P450 (CYP) 14-alpha-demethylase (CYP51), an enzyme key to fungal cell wall development. In vertebrates, several other CYP enzymes also are targets for conazoles, potentially disrupting processes such as xenobiotic metabolism and sex steroid synthesis. Propiconazole is of particular interest because it is a current-use pesticide, due to undergo reregistration by the US Environmental Protection Agency (USEPA) in the near future, and also is one of about 60 chemicals being tested in the USEPA Tier 1 screening program for endocrine disrupting chemicals. Fathead minnows (Pimephales promelas) were exposed to 0, 5, 50, 500, 1000 µg propiconazole/L in a 21-d study that evaluated apical reproductive endpoints (fecundity, fertility, hatch), as well as bioconcentration of the chemical in the fish. In addition, cholesterol, triglycerides, vitellogenin (VTG), and sex steroid (testosterone [T], 17â-estradiol [E2]) concentrations were determined in the plasma of the fish, and changes in expression of several gonadal and hepatic genes involved to steroid synthesis, and cholesterol and xenobiotic metabolism were measured. Plasma E2 and VTG concentrations in females were significantly reduced by exposure to propiconazole, and egg production was decreased in a concentration-dependent fashion in the 500 and 1000 µg/L treatment groups. These effects coincided with inhibition of E2 synthesis by propiconazole by ovary explants in in vitro experiments. We also observed a compensatory response in females exposed to propiconazole, manifested as increased gonad weight and up-regulation of genes coding for key steriodogenic proteins, including CYP19 (aromatase), CYP17 (hydroxylase/lyase), CYP11A (cholesterol side-chain-cleavage), and steroid acute regulatory protein. Effects on endocrine function in males were less pronounced than in females, although there was a significant increase in relative testis weight. Results of these studies provide important data specific to the potential endocrine and reproductive toxicity of propiconazole in fish and, more generally, to the further derivation/validation of AOPs for the reproductive effects of steroid synthesis inhibitors in fish.

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