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Tebuconazole disrupts steroidogenesis in Xenopus laevis
Rikke Poulsen1, Xuan Luong2, Martin Hansen3
1Laboratory for Integrative Studies in Amphibian Biology, Department of Integrative Biology, University of California, Berkeley, CA 94720, USA; Toxicology Laboratory, Section of Advanced Drug Analysis, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Tebuconazole disrupts frog steroidogenesis, altering testosterone and estradiol levels. Higher doses suppressed estradiol, while lower doses affected testosterone production, suggesting complex endocrine disruption mechanisms.
Area of Science:
- Endocrinology
- Environmental Toxicology
- Aquatic Biology
Background:
- Steroidogenesis is crucial for reproductive health.
- Fungicides like tebuconazole can act as endocrine disruptors.
- African clawed frogs (Xenopus laevis) are sensitive models for environmental contaminants.
Purpose of the Study:
- To investigate the mechanism of tebuconazole-induced disruption of steroidogenesis in Xenopus laevis.
- To determine dose-dependent and time-dependent effects of tebuconazole on hormone levels.
- To explore the impact of tebuconazole on specific steroidogenic enzymes.
Main Methods:
- Controlled 27-day exposure of Xenopus laevis to tebuconazole.
- Quantification of tebuconazole in tissues using LC-MS/MS.
- Measurement of steroid hormones (testosterone, dihydrotestosterone, 17β-estradiol) in plasma and gonads using LC-MS/MS and GC-MS/MS.
- Assessment of androgen levels via radioimmunoassay.
- Analysis of CYP17 enzyme expression.
Main Results:
- Tebuconazole bioconcentrated in frog tissues (BCF up to 238).
- Low-dose tebuconazole (0.1μgL⁻¹) decreased plasma testosterone and dihydrotestosterone.
- High-dose tebuconazole (100 and 500μgL⁻¹) increased plasma testosterone and dihydrotestosterone initially, but decreased 17β-estradiol.
- Prolonged high-dose exposure persisted in suppressing 17β-estradiol and increased gonadal testosterone, dihydrotestosterone, and CYP17 expression.
Conclusions:
- Tebuconazole exhibits complex, dose-dependent effects on frog steroidogenesis.
- Low doses may inhibit CYP17, while high doses appear to suppress CYP19, leading to altered androgen and estrogen levels.
- Observed increases in gonadal androgens may indicate compensatory mechanisms in response to endocrine disruption.
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