Fluoxetine induces changes in the testicle and testosterone in adult male rats exposed via placenta and lactation

Abstract

Fluoxetine is a selective serotonin reuptake inhibitor used to treat depression in pregnant and nursing women. However, recent studies have shown adverse effects in the male reproductive system after fluoxetine treatment. Aiming to analyze the extent of damage caused by fluoxetine in the testicle and safe doses for treatment during the perinatal period, the present study analyzed the effects of in utero exposure and exposure during lactation to fluoxetine in spermatogenesis of male rat offspring in adulthood. Wistar rat dams were orally treated with fluoxetine (5, 10, and 20 mg/kg) from 13 days of gestation to lactation day 21 and their offspring were analyzed at 90 days old. Results showed a reduction in the weight of testes (16%), epididymis (28%), and seminal glands (18%) in animals exposed to fluoxetine 20 mg/kg compared to the control. Seminal gland weight was also reduced 25% and 30% in animals exposed to 5 mg/kg and 10 mg/kg fluoxetine, respectively. Body weight of animals exposed to 20 mg/kg fluoxetine was reduced from post-natal day 9 to 36 compared to controls but from the post-natal day 9 to 36 there was no statistical difference. The volume of seminiferous epithelium reduced 17% and the total volume of Leydig cells reduced 30% in the group exposed to fluoxetine at 20 mg/kg. Furthermore, Leydig cells volume reduced 29% in the 5 mg/kg group. The length of the seminiferous tubules reduced 17% and daily sperm production per testicle also reduced 18% in animals exposed to the highest dose of fluoxetine compared to controls. The individual area of Leydig cells increased 7% and plasma testosterone increased 49% in animals exposed to fluoxetine at 20 mg/kg. In conclusion, exposure to 20 mg/kg fluoxetine via the placenta and during lactation may change testosterone and testicular parameters important for sperm production and male fertility in adulthood.

Recovery effect of pre-germinated brown rice on the alteration of sperm quality, testicular structure and androgen receptor expression in rat model of depression

“…On the other hand, rat testicular weight was decreased after high dose serotonin administration over 4 days (Hedger et al ., ). In addition, a reduction in testicular weight has been reported in adult male rats exposed to an SSRI in early life via the placenta and during lactation (de Oliveira et al ., ; Monteiro Filho et al ., ). These could indicate that testicular weight is affected when animals undergo long‐term stress stimulation, as well as when exposed to antidepressants.…”

The antidepressant Sertraline inhibits CatSper Ca2+ channels in human sperm

“…Supporting this notion, previous studies suggested that SSRIs reduce male fertility by affecting semen quality (reviewed by Norr et al , 2016 ; Sylvester et al , 2019 ; Beeder and Samplaski, 2020 ). Treatment of rodents with SSRIs reduced the sperm count, sperm motility, testicular weight, length of seminiferous tubules, and, thereby, male fertility ( Bataineh and Daradka, 2007 ; Attia, and Bakheet, 2013 ; Monteiro Filho et al , 2014 ; Galal et al , 2016 ; Lyons et al , 2016 ; Atli et al , 2017 ). In men, intake of SSRIs was associated with reduced sperm concentration, a higher number of morphologically abnormal sperm, and an increase in DNA fragmentation.…”

Estrogenic/antiestrogenic activity of selected selective serotonin reuptake inhibitors

“…Rodent studied demonstrated that FLX can affect sexual brain differentiation, sexual behavior, testicular development and sperm production in rat offspring exposed in utero and/or through lactation [ 27 , 28 , 29 , 30 ]. Mueller et al showed that FLX can act as an estrogen receptor agonist both in vitro and in vivo [ 3 ].…”