P-62: Damage to Sperm DNA and Protamine Deficiency Induced by Risperidone in NMRI Mice

Background: Antipsychotic medication use is a common cause of hyperprolactinemia that shown to have adverse effects on male fertility. Risperidone is a combined serotonin/dopamine receptor antagonist that can cause elevations in prolactine level. Its mechanism of cytotoxic effects on testicular germ cells is not fully understood. In the present study we sought to elucidate the impact of risperidone on sperm DNA integrity and chromatin quality in male mice. Materials and Methods: 8-week old male NMRI mice were randomly assigned to two groups as control-sham and test groups. Risperidone was administered by gavage once daily for 45 consecutive days in dose of 3.2 mg/kg. The control group just received vehicle. At the end of the study period the animals were euthanized by decapitation. Sperms were removed from cauda epididymis and analyzed for chromatin integrity and DNA damage. Results: The level of abnormal single-stranded sperm DNA in Risperidone- treated mice was significantly higher than that of control group. The percentage of sperms with protamine deficiency in treated group was higher than those of control group. Conclusion: Current findings illustrated that risperidone induced its detrimental effects by protamine impairment which was able to increase DNA susceptibly for damages.