Chronic administration of nonsteroidal-antiinflammatory drugs (NSAIDS): effects upon mouse reproductive functions

Although nonsteroidal-antiinflamatory drugs (NSAIDs) are widely employed, reproductive side effects of prostaglandins long-term inhibition remain unknown. The objective of the present study was to evaluate the effects of chronic low/moderate NSAIDs doses upon mice reproductive functions. Male or female mice were injected (i.p. for 60 or 35 days respectively) with: ibuprofen doses A, B or C (0.56, 1.12 or 1.68 mg/100 g/day respectively) or piroxicam doses A, B or C (0.028, 0.056 or 0.084 mg/100 g/day respectively). Parameters evaluated were: a) in females, spontaneous and induced ovulation, oocyte maturity and spermatozoa migration through genital tract, b) in males, epididymal spermatozoa concentration, motility, viability, resistance to hypoosmotic shock, acrosomal status and membrane maturity and c) in both genders, in vitro and in vivo fertilization, reproductive hormones plasma levels and cyclooxigenase inhibition in reproductive tissues. In females ibuprofen (dose A) elicited a significant reduction in spontaneous and induced ovulation rates and piroxicam (dose A) diminished the concentration of spermatozoa found in the uterus after mating. Males treated with ibuprofen (dose B) showed a reduction in the in vitro fertilization ability. Our data reveal that chronic administration of ibuprofen or piroxicam can exert detrimental effects upon reproductive physiology, which depends on the doses and/or the drug employed.