Fluoxetine treatment of prepubertal male rats uniformly diminishes sex hormone levels and, in a subpopulation of animals, negatively affects sperm quality

Abstract

Fluoxetine (Flx) is a selective serotonin reuptake inhibitor that alters the male reproductive system when administered at the adult stage or after maternal exposure. In the present study we evaluated the effects of Flx administration on reproductive parameters during juvenile–peripubertal development when treated male rats reached adulthood. Groups of rats were treated daily with Flx (5 mg kg−1, i.p.) or saline (0.9% NaCl), or were left untreated. Rats were treated between 30 and 53 days of age and were killed at 65 days of age. Serotonin concentrations were determined in the hypothalamus, hypophysis and testis. Gonadotrophins, sex steroids and sperm quality (membrane integrity, sperm with functional mitochondria, sperm density, sperm motility and morphological abnormalities) were also evaluated. Flx did not affect bodyweight, but significantly diminished LH, FSH, progesterone and testosterone serum concentrations. After graphical analysis, a subgroup of rats was identified whose sperm quality parameters were greatly affected by Flx. In the present study we show that Flx administered to juvenile rats disrupts the hypothalamic–hypophyseal–testicular axis and its effects on sperm quality are not homogeneous in adults. In contrast, Flx altered concentrations of gonadotrophins and sexual steroids in all treated rats. These results suggest caution should be exercised in the prescription of Flx to prepubertal males.