Damaging Effects of Cisplatin on Mouse Spermatozoa

Abstract

The effect of cis-diamminedichloroplatinum (cisplatin: CDDP) on mouse spermatozoa was evaluated quantitatively by means of equilibrium sedimentation in Percoll. CDDP was administered subcutaneously at doses of 1, 3, and 10 mg/kg/week for 5 weeks. After different periods (1, 3, and 10 weeks) without CDDP, the quality of epididymal sperm was evaluated by sperm count, motility, morphology of sperm, and the apparent density of sperm. At 10 mg/kg dose, about 80% mortality occurred during the administration period. There were no sperm even 10 weeks after discontinuing CDDP. With the 3 mg/ kg dose, sperm count, motility, and normal morphology of sperm declined after 1 and 5 weeks, but recovered to the control level after 10 weeks. The sperm distribution profiles in the Percoll gradient were quite different among the groups. The control sperm showed two separated peaks in the gradient, whereas the peak of sperm at 1 and 3 mg/kg were shifted forward to lighter apparent density. CDDP causes a reduction in sperm apparent density and impairs semen quality in mice.

Evaluation of testicular toxicology of doxorubicin based on microarray analysis of testicular specific gene expression

“…The doses of doxorubicin and the test schedule were determined by a previous study of their damaging effects on mouse spermatozoa (Oshio et al, 1987). Previous studies have shown that a decrease in sperm motility was induced by administration of 0.3 mg/kg of doxorubicin hydrochloride, three times a week for 6 weeks (Oshio et al, 1987(Oshio et al, , 1989 but not by 0.1 mg/ kg of doxorubicin hydrochloride. The weight of reproductive organ was not affected in the low-dose treated group but was significantly lighter in the high-dose treated group.…”

“…Mice in the control group received only saline on the same schedule as the treated groups. After a washout period of 46 days, the mice were weighed and sacrificed under hyperanesthesia using diethyl ether, as a simple anesthetic compound used in a previous study (Oshio et al, 1987), to obtain tissues of testis, epididymis, accessory reproductive organs (prostate, seminal vesicles and coagulating glands) and blood samples. The doses and study protocol followed the previous study to examine testicular toxicity by Oshio et al (1987).…”

“…Sperm suspension was collected from the cauda epididymis by mincing in HEPES-buffered TYH medium (pH 7.4) and prepared for examination of sperm motility and morphology as previously described (Oshio et al, 1987(Oshio et al, , 1990. To quantitate the sperm motility, sample aliquots of 20 μl were placed on a hemocytometer and more than 200 sperms were observed and counted under a phase contrast microscope (BX51, Olympus Co., Tokyo, Japan) and a video system.…”

“…ty, sperm morphology and sperm count and by the histological examination of Leydig cells, Sertoli cells and spermatogenic cells (Oshio et al, 1987;Matsui and Takahashi, 1999;Kato et al, 2001). The assays are useful for determine if the substances influence detrimental effects on male reproductive system; however, by only using these examinations, it is difficult to understand the precise mechanism of testicular toxicity.…”

“…We attempted to establish a method that can evaluate the overview of testicular toxic mechanisms using a tissue-specific microarray, Mouse Testis2. The effects of doxorubicin, a typical chemotherapeutic drug for cancer known to be toxic for testicular functions damage (Meistrich et al, 1982;Oshio et al, 1987), were analyzed on testis tissue using microarray technology. The results were compared with previous reports on the mechanisms of testicular toxicity of doxorubicin.…”