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Updated: Jun 11, 2025

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Trifluoperazine effect on human sperm: The accumulation of reactive oxygen species and the decrease in the

Houpeng Wang1, Cheng Cheng2, Jing Ding2

  • 1Jiangxi Provincial Key Laboratory of Disease Prevention and Public Health, Jiangxi Medical College, Nanchang University, Nanchang 330006, China; School of Public Health, Jiangxi Medical College, Nanchang University, China.

Reproductive Toxicology (Elmsford, N.Y.)
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Trifluoperazine (TFP), an antipsychotic, may harm male fertility. High TFP concentrations reduced sperm viability by increasing reactive oxygen species (ROS) and decreasing mitochondrial membrane potential (MMP).

Keywords:
Drug repurposingHuman semen qualityIn vitroIntracellular calcium concentrationTrifluoperazine

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Area of Science:

  • Reproductive Toxicology
  • Pharmacology

Background:

  • Antipsychotic drug use is linked to reduced human sperm quality.
  • Trifluoperazine (TFP), a common antipsychotic, is being investigated for anticancer properties.
  • The impact of TFP on human sperm quality is not well understood.

Purpose of the Study:

  • To investigate the effects of TFP on human sperm function and physiological parameters in vitro.
  • To determine the concentration-dependent toxicity of TFP on sperm.

Main Methods:

  • Human sperm were co-cultured with various concentrations of TFP (12.5, 25, 50, and 100 μM).
  • Sperm function and physiological parameters, including reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), viability, motility, penetration ability, capacitation, and acrosome reaction, were assessed.

Main Results:

  • TFP concentrations of 50 μM and 100 μM increased ROS and decreased MMP, leading to reduced sperm viability.
  • 25 μM TFP inhibited sperm penetration ability, total motility, and progressive motility.
  • Lower TFP concentrations (12.5 and 25 μM) increased intracellular calcium ([Ca2+]i) but did not affect capacitation or acrosome reaction, possibly due to lack of increased tyrosine phosphorylation.

Conclusions:

  • TFP can induce male reproductive toxicity.
  • Mechanisms of toxicity include ROS accumulation and decreased MMP in human sperm.
  • These findings highlight potential risks of TFP use on male fertility.