Reproductive toxicology of methyldopa in male F344/N rats.
Methyldopa, a widely used antihypertensive drug, was administered to male Fischer 344/N rats by gavage 5 days/week for 65 days at dosages of 0, 50, 100, 200, or 400 mg/kg. Decreased body weight was seen in treated animals. After mating to untreated female Fischer 344/N rats on days 57-61, the male rats were necropsied (days 65-67) and reproductive toxicity was measured by sperm count, sperm motility, organ weights, hormone levels and histologic evaluation of the testis. Decreased fertility was seen in males dosed with 200 or 400 mg/kg methyldopa. Decreases were also seen in sperm count, sperm motility, apparent number of late spermatids, and plasma testosterone levels in males in the 200 and 400 mg/kg groups. This alternation of reproductive function in male rats was found to be reversible after a 13-week recovery period without dosing. The marked decrease in circulating testosterone levels following methyldopa treatment at 200 or 400 mg/kg may have contributed to the reproductive toxicity of this drug.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D008750:Methyldopa / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012098:Reproduction / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013739:Testosterone / Q000097:blood
D013739:Testosterone; D008750:Methyldopa