The effect of fluoxetine on spermatogenesis and spermatogonial stem cells self-renewal in adult male rats

Fluoxetine (FLX) application as a selective serotonin reuptake inhibitor (SSRI) drug that accompanies side effects including reproductive dysfunctions. The current study was designed to explore the effects of FLX on rat spermatogenesis as well as spermatogonial stem cells self-renewal through evaluation of glial cell line-derived neurotrophic factor family receptor alpha-1 (GFRα1) expression at mRNA level in testicular tissue.
Adult male Wistar rats were randomly allocated into experimental and control groups. The experimental group was subdivided into two groups which received 5 mg/kg/day and 10 mg/kg/day of FLX orally for 48 days. Testicular tissue samples were collected 24 hours after the last treatment and histological assessments and reverse transcription polymerase chain reaction were done to analyze spermatogenesis and mRNA expression of GFRα1, respectively.
Treatment with FLX caused spermatozoa maturation arrest in a dose-dependent manner as was evident by significant decreases in spermatogenic indices. Moreover, FLX administration at a dose of 10 mg/kg/day resulted in significant reduction in mRNA expression of GFRα1 in testicular tissue.
These findings suggest that FLX induces male reproductive toxicities via disruption of spermatogonial stem cells self-renewal, bringing about the necessity of more researches about the precise mechanisms of SSRI antidepressants-induced spermatogenic failures.