Effects of adriamycin, an anticancer drug showing testicular toxicity, on fertility in male rats.
Adriamycin (ADR), an anticancer drug,was intravenously administered to Slc:SD male rats at doses of 0, 1 and 2 mg/kg once a week for 4 or 9 weeks before pairing, and the treatment period and parameters suitable for detection of male fertility disorder were examined. No adverse effects were observed on the copulation index, fertility index and spermatozoa, but testicular weights were low in the 1 and 2 mg/kg groups after 4-week treatment. In the 2 mg/kg group after 9-week treatment, 11 of 12 males had died or became moribund, and no successful pregnancies were observed. The males in the 1 and 2 mg/kg groups after 9-week treatment had decreased weights of the genital organs, an extremely decreased number of sperm and low sperm motility as well as a low implantation rate and a decreased number of live fetuses. Microscopically, the numbers of spermatogonia were decreased in the 1 and 2 mg/kg groups after 4-week treatment, whereas the numbers of even spermatozoa were diminished and genital organs showed atrophy after 9-week treatment. These results indicate that 4-week treatment before pairing is sufficient to detect effects of ADR on the testis, especially on spermatogonia, and that microscopic findings and testis weight are appropriate parameters for detection of male fertility disorders.
Imahie
H
H
Safety Research Laboratory, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
Adachi
T
T
Nakagawa
Y
Y
Nagasaki
T
T
Yamamura
T
T
Hori
M
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity*; D004334:Drug Administration Schedule; D005260:Female; D005298:Fertility / Q000187:drug effects; D007248:Infertility, Male / Q000139:chemically induced* / Q000175:diagnosis / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin