Effects of a new platinum complex on male fertility in rats--collaborative work to determine the optimal period and optimal parameters to detect effects on male fertility in rats.
To assess the testicular toxicity induced by compound C, a new platinum complex being developed as an anti-cancer drug, the substance was intravenously administered to male rats at doses of 1, 3 and 10 mg/kg/day for 4 weeks and at doses of 0.3, 1 and 3 mg/kg/day for 9 weeks. Males were cohabited with non-treated females after these treatment periods and at sacrifice the genital organ weights and number of sperm in the testis were recorded and a histopathological examination performed. The females were sacrificed on day 13 of gestation and the numbers of corpora lutea, implantations and resorptions were counted. In the 4 weeks treatment 10 mg/kg/day group, the testis weight increased while the weights of the epididymides, seminal vesicles and prostate decreased significantly, and the number of sperm was significantly decreased. Extension of seminiferous tubules, vacuolization of spermatocytes, spermatids and Sertoli cells, and degeneration of spermatocytes and spermatids were observed by histopathological examination. Copulation and impregnation were not affected by treatment but the implantation rate was significantly decreased in the 10 mg/kg/day group. These results show that compound C has testicular toxicity like other platinum complexes and that organ weight, number of sperm, number of implantation and histopathological examination are useful for detection purposes. Treatment with compound C for 9 weeks did not affect male reproductive function in spite of severe general toxicity. This suggests that testicular toxicity should be detected after 4 weeks rather than 9 weeks treatment.
Mizoguchi
K
K
Toxicology Laboratory, Chugai Pharmaceutical Co., Ltd., Nagano, Japan.
Tsuno
T
T
Hara
H
H
Tanaka
N
N
Igarashi
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005298:Fertility / Q000187:drug effects*; D007248:Infertility, Male / Q000139:chemically induced* / Q000175:diagnosis; D008297:Male; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000187:drug effects / Q000473:pathology
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds