Steroidogenesis and aromatase increase in Leydig cells: a possible target for spermatogenesis and sperm parameters changes induced by venlafaxine

Venlafaxine (norepinephrine and serotonin reuptake inhibitor) effects on testicular functions were evaluated. Adult male rats received venlafaxine (30mg/kg BW) or saline for 35 days. Morphology and motility of spermatozoa were evaluated. Seminiferous tubule/epithelial areas and Leydig cell nuclear diameter (LCnu) were measured; the number of Sertoli cells (SCN) and spermatogonia (SgN) were quantified. Serum testosterone, StAR (steroidogenesis marker), aromatase immunoexpression, cell death (TUNEL) and ndrg2 expression (specific for LC and apoptosis) were evaluated. Venlafaxine increased LCnu, aromatase and StAR immunoexpression as well as serum testosterone. A decrease in SgN, SCN and increased germ cell death was in agreement with a reduction in tubular/epithelial areas and changes in sperm parameters. Ndrg2 overexpression correlated with LC hypertrophy and germ cell death. This overexpression corroborates increased aromatase (estrogen levels), which may be associated with changes in spermatogenesis. Since norepinephrine plays a role in steroidogenesis, the effect of this neurotransmitter on LC requires further investigation.