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 (5mgkg-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.

Dopamine receptor agonist rotigotine-loaded microspheres ameliorates sexual function deteriorated by fluoxetine in depression rats

“…A previous study reported that fluoxetine administration decreased the luteinizing hormone and testosterone levels in intact rats ( Ayala et al, 2018 ). The present study showed that fluoxetine also diminished luteinizing hormone and testosterone levels in bulbectomized male rats.…”

Role of serotonin, estrogen, and TNF‐α in the paroxetine‐impaired steroidogenesis and testicular macrophages polarization

“…Oxidative stress is one of the main causes of male infertility since testicular germ cells are vulnerable to reactive oxygen species (ROS) and lipid peroxidation, 22,23 which increases cytotoxic aldehydes, as MDA, causing cellular dysfunction and death. 73,74 Moreover, the increase of RNS derived from the decomposition of NO impairs LC function and induces germ cell apoptosis. 23,25,75 Therefore, the high index of TUNEL positive-germ cells in the paroxetine-treated animals may also be related to ROS-and RNS-induced apoptosis.…”