Paternal dapoxetine administration induced deterioration in reproductive performance, fetal outcome, sexual behavior and biochemistry of male rats

Int J Impot Res. Nov-Dec 2015;27(6):206-14. doi: 10.1038/ijir.2015.16. Epub 2015 Sep 24.

Abstract

Dapoxetine, a selective serotonin reuptake inhibitor, is considered an antidepressant drug and has been developed for the treatment of premature ejaculation. Hence the objective was to assess whether dapoxetine administration to male rats adversely affect sexual behavior and pregnancy outcomes after mating with untreated female rats. Proven fertile male rats were gavaged with 0, 2.0, 4.0 and 8.0 mg dapoxetine per kg body weight (bw) per day (DC, DI, DII and DIII groups, respectively) for 70 days prior to mating with untreated female rats. Weight gain, organ weights and feed consumption were decreased significantly in the DII and DIII groups. A significant decline in the number of spermatozoa in the DII and DIII groups is attributed to a significant decrease in testosterone, luteinizing hormone and follicle-stimulating hormone. Levels of prolactin were significantly increased in the DII and DIII groups. Rats treated with a high dose of dapoxetine (8.0 mg kg(-1)) showed a significant inhibition in sperm motility and increment in sperm abnormalities. There was a pronounced decrease in fertility index in females mated with males treated chronically with 4.0 and 8.0 mg per kg bw dapoxetine. In addition, the treatment markedly increased the number of fetal resorptions in female rats impregnated by males in the DII and DIII groups reflecting their infertility. The number of implantation sites and the number of viable fetuses were also notably decreased in female rats impregnated by males given 4.0 or 8.0 mg kg(-1) dapoxetine. These findings suggest that the long-term dapoxetine at high dosages causes failure of the fertilization or successful impregnation of the females mated with dapoxetine-treated male rats, which were clearly able to copulate. A detrimental effect of dapoxetine on fertility parameters was also revealed.

MeSH terms

  • Animals
  • Benzylamines / administration & dosage
  • Benzylamines / toxicity*
  • Dose-Response Relationship, Drug
  • Female
  • Fertility / drug effects
  • Follicle Stimulating Hormone / blood
  • Luteinizing Hormone / blood
  • Male
  • Naphthalenes / administration & dosage
  • Naphthalenes / toxicity*
  • Paternal Exposure*
  • Pregnancy
  • Pregnancy Outcome*
  • Rats
  • Rats, Wistar
  • Reproduction / drug effects*
  • Serotonin Uptake Inhibitors / toxicity
  • Sexual Behavior, Animal / drug effects*
  • Sperm Count / veterinary
  • Sperm Motility / drug effects
  • Spermatozoa / drug effects
  • Spermatozoa / physiology
  • Testosterone / blood

Substances

  • Benzylamines
  • Naphthalenes
  • Serotonin Uptake Inhibitors
  • Testosterone
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • dapoxetine