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Fluoxetine Mitigates Human Sperm Quality by Disrupting the Antioxidant Defense System and Altering the Expression of

Zahra Roostaee1, Malek Soleimani Mehranjani2, Ebrahim Cheraghi3

  • 1Department of Biology, Faculty of Science, Arak University, PO Box 384-817758, Sardasht, Arak, 384817758, Iran.

Reproductive Sciences (Thousand Oaks, Calif.)
|January 9, 2025
PubMed

Insights

Fluoxetine negatively impacts human sperm quality by increasing oxidative stress and apoptosis, reducing motility and viability. This highlights potential reproductive concerns for men of reproductive age using this antidepressant.

Area of Science:

  • Reproductive Biology
  • Pharmacology
  • Biochemistry

Background:

  • Fluoxetine, an SSRI antidepressant, increases brain serotonin but can cause sexual side effects.
  • Oxidative stress and altered sex hormone homeostasis are implicated in fluoxetine's side effects.
  • Men of reproductive age are a key demographic affected by these potential reproductive impacts.

Purpose of the Study:

  • To investigate the in vitro effects of fluoxetine on human sperm biochemical markers.
  • To assess fluoxetine's impact on key sperm parameters and cellular integrity.
  • To examine fluoxetine's influence on apoptotic pathways and oxidative stress markers in sperm.

Main Methods:

  • Semen samples from 30 fertile men were divided into control and fluoxetine-treated groups.
  • Evaluated sperm parameters including motility, viability, mitochondrial membrane potential (MMP), and acrosome reaction.
  • Assessed DNA fragmentation, chromatin integrity, total antioxidant capacity (TAC), reactive oxygen species (ROS), and expression of apoptosis-related genes (CASPASE8, CASPASE9, BAX, BCL2).

Main Results:

  • Fluoxetine significantly reduced sperm motility, viability, MMP, acrosome and chromatin integrity, and TAC.
  • Increased percentages of non-progressive motility, sperm DNA fragmentation, MDA, and ROS were observed in the fluoxetine group.
  • Fluoxetine significantly altered the expression of apoptosis-related genes and proteins, increasing pro-apoptotic markers (CASPASE8, CASPASE9, BAX) and decreasing anti-apoptotic marker (BCL2).

Conclusions:

  • Fluoxetine impairs human sperm quality by inducing oxidative stress and increasing apoptosis.
  • The drug lowers total antioxidant capacity while increasing reactive oxygen species in sperm.
  • Fluoxetine's pro-apoptotic effects on sperm warrant careful consideration in reproductive-aged men.
Keywords:
Apoptotic genesFluoxetineHuman spermOxidative stress

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