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MALE ANTIFERTILITY COMPOUNDS: U-5897 AS A RAT CHEMOSTERILANT

Summary.: U-5897 (3-chloro-1,2-propanediol) is an effective male rat chemosterilant. Sterility results from a lesion in the initial segment of the caput epididymidis. Minimal amounts required to develop lesions consistently are daily oral doses of 35 mg/kg body weight or one 45 mg/kg dose. The immediate consequences of the lesion are sperm blockage in ductuli efferentes and testicular swelling. Fluid accumulation in the testis causes pressure degeneration of the germinal epithelium. Testicular damage does not include morphological or functional (coitus, vaginal plugs, limited spermatogenesis) impairment of Leydig cells. U-5897 is thought to cause local ischaemia, with resultant epithelial desquamation which blocks the caput epididymidis. This is followed by the formation of spermatocoeles, sperm granulomata, and fibrosis. Males made sterile with such a lesion had normal libido with seventy-one matings out of seventy-seven opportunities (92%) over a 64-day period. Adult rats given a single oral dose of 90 to 100 mg/kg of U-5897 still had lesions blocking sperm passage when killed at 3-month intervals over at least 12 months. Although sterile, they continued to mateand enjoyed good general health. Testes were small due to many non-functional seminiferous tubules but spermatogenesis continued in a few tubules. Compound acceptance and potency, route and length of administration, and biological effectiveness make U-5897 and the concept of a male chemosterilant worthy of practical consideration.

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