title: The effects of chronic administration of pyrimethamine on spermatogenesis and fertility in male rats.
abstract: The present study examines whether the antifertility effects of pyrimethamine (PYR), an inhibitor of dihydrofolate reductase, are mediated by a reduction in intratesticular testosterone (T) concentrations or whether PYR exerts its effect by a cytotoxic insult to spermatogenic cells that is independent of intratesticular testosterone. Adult male rats were treated daily with 100 mg/kg (n = 16) or 400 mg/kg (n = 16) of PYR in honey for 8 weeks. Control rats (n = 16) received honey without PYR. Eight weeks after treatment, five rats from each PYR-treated group and five control rats were mated with normal cycling female rats, and fertility was assessed. These rats were euthanized after the fertility trial; testis weight, testicular sperm, and epididymal sperm counts were determined, and serum levels of T, LH, FSH, and seminiferous tubule fluid T (STF-T) concentrations were measured by RIA. Testes from three rats per group were perfusion-fixed for histological evaluation. PYR was discontinued in the remaining rats for 8 weeks and similar parameters were evaluated after 8 weeks of recovery. PYR (100 mg/kg/day) treatment for 8 weeks did not have any effects on organ weights, testicular and epididymal sperm counts, and hormone levels when compared to controls. In contrast, PYR (400 mg/kg/day) treatment significantly reduced testis and epididymis weights, testicular and epididymal sperm counts, and fertility. Despite these effects, serum T, LH, FSH, and STF-T concentrations were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Obstetrics and Gynecology, University of Colorado Health Sciences Center, Denver 80224.
authors.forename: C A
authors.initials: CA
authors.lastname: Awoniyi
authors.forename: V
authors.initials: V
authors.lastname: Chandrashekar
authors.forename: B S
authors.initials: BS
authors.lastname: Hurst
authors.forename: W K
authors.initials: WK
authors.lastname: Kim
authors.forename: W D
authors.initials: WD
authors.lastname: Schlaff
mesh_terms: D000818:Animals; D004822:Epididymis / Q000187:drug effects; D005298:Fertility / Q000187:drug effects*; D005640:Follicle Stimulating Hormone / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011739:Pyrimethamine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013076:Sperm Count / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects; D013737:Testis / Q000033:anatomy & histology / Q000187:drug effects; D013739:Testosterone / Q000378:metabolism; D013997:Time Factors
chemical_list: D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D011739:Pyrimethamine