Short-term effects of N'N-bis(dichloroacetyl)-1,8-octamethylenediamine (WIN 18446) on the testes, selected sperm parameters and fertility of male CBA mice

Abstract

N'N-bis(dichloroacetyl)-1,8-octamethylenediamine (WIN 18446), the most potent of the diamines and one of the least amoebicidal agents, was shown to exert a specific effect on the testes of CBA mice, while the Leydig cells were unaffected. Spermatogenesis was severely affected after a 42-day treatment period with 125 mg WIN 18446/kg body weight. Large multinucleated cells, vacuolization and the absence of sperm within the testes were evident in most seminiferous tubules. After 15 days of withdrawal of WIN 18446, there was a slight recovery of spermatogenesis and after withdrawal of 42 days a marked recovery of spermatogenesis. The normality or abnormality of this spermatogenic cycle could be evaluated using the semi-quantitative Stages program. There was a significant decrease in the diameters of seminiferous tubules of WIN 18446 treated mice, however an almost complete recovery was evident after 42 days of withdrawal of WIN 18446. A significant decrease in sperm concentration and sperm morphology was observed for the WIN 18446 treated mice. Various sperm motion parameters were assessed for the different treatment groups and compared to the control group. The female and male fertility indices were assessed and compared for the different treatment groups. Complete recovery of the above-mentioned parameters was evident after 42 days of withdrawal from WIN 18446, and this confirms its potential as a possible contraceptive for animal populations.