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Gemfibrozil and carbamazepine decrease steroid production in zebrafish testes (Danio rerio).

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Chronic exposure to gemfibrozil (GEM) and carbamazepine (CBZ) in zebrafish reduced androgen levels and reproductive output. Both pharmaceuticals impaired testicular 11-ketotestosterone (11-KT) production, with CBZ potentially affecting steroidogenic enzymes.

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Area of Science:

  • Environmental toxicology
  • Endocrinology
  • Aquatic toxicology

Background:

  • Gemfibrozil (GEM) and carbamazepine (CBZ) are prevalent environmental pharmaceuticals.
  • Chronic exposure to these compounds has been linked to reduced androgen levels and impaired fish reproduction in laboratory settings.

Purpose of the Study:

  • To investigate the effects of GEM and CBZ on testicular steroid production in zebrafish.
  • To identify the specific step in the steroidogenic pathway affected by each pharmaceutical.

Main Methods:

  • Adult zebrafish were chronically exposed to GEM and CBZ via water.
  • Testicular 11-ketotestosterone (11-KT) production was assessed using ex vivo cultures with various stimulations (hCG, 25-OH cholesterol, pregnenolone).
  • Chemical analysis confirmed exposure concentrations.

Main Results:

  • Chronic exposure to GEM and CBZ (at approximately 17.5 and 11.2 μg/L, respectively) reduced reproductive output and lowered 11-KT levels.
  • Ex vivo testicular cultures showed reduced basal and stimulated 11-KT production in exposed zebrafish compared to controls.
  • hCG-stimulated 11-KT production was significantly lower in both GEM and CBZ groups.
  • 25-OH cholesterol and pregnenolone stimulation revealed reduced 11-KT production in the CBZ group but not the GEM group compared to controls.

Conclusions:

  • Chronic GEM and CBZ exposure negatively impacts testicular 11-ketotestosterone production in zebrafish through direct effects.
  • GEM exposure does not appear to significantly disrupt the biochemical processes of steroid production.
  • CBZ exposure may impair steroidogenic enzyme expression or function, affecting 11-KT synthesis.