Disruption of the Metabolism, Motility and Morphology of Spermatozoa by Injection of a-Chlorohydrin Into Rams

Abstract

Aust. J. Bioi. Sci., 1976, 29, 545-55 Ejaculated spermatozoa from rams given intramuscular injections of <x-chlorohydrin (25 mg/kg, daily for 5 days) were studied. Respiratory and glycolytic activity of the spermatozoa was almost entirely suppressed within 1 day and motility had decreased within 4 days of the first injection. Morphologically abnormal spermatozoa appeared in ejaculates after 2 weeks. The most common abnormality was an increase in the number of spermatozoa with looped or bent tails. There was little change in the fructose or amino acid concentration of the seminal plasma. All effects of <x-chlorohydrin were fully reversible. It is suggested that the initial primary mode of action of <x-chlorohydrin is to disrupt the metabolism of spermatozoa in the cauda epididymis.

Inhibition of the metabolism of ram spermatozoa by derivatives of α‐chlorohydrin

“…a-Chlorohydrin significant reduction in all the metabolic parameters of the ram spermatozoa, ie, oxygen consumption, C 0 2 production, fructose utilization, lactic acid accumulation, and dpm C14 0 2 . The total absence of lactate accumulation clearly demonstrated the extent of the inhibition of glycolysis, and a similar effect was seen with spermatoza collected from rams after administration of a-chlorohydrin [Brown-Woodman and White, 1976;Brown-Woodman et al, 19781.…”

“…This value was substantially reduced as the concentration of a-chlorohydrin increased. When a-chlorohydrin is injected into rats at a daily dose of 5 mg/kg, fertility is lost completely [Brown-Woodman et al, 1976;19791. Assuming even distribution of a-chlorohydrin over 80% of the body, spermatozoa in the epididymis would be exposed to an a-chlorohydrin concentration of 0.04 mM. However, the levels could be higher, since a-chlorohydrin has been shown to be concentrated in the cauda epididymis [Crabo and Appelgren, 19701. Compound I reduced at a concentration of compound I below 10 mM (Table 2).…”

“…However, the fact that compound I was less effective than a-chlorohydrin in depres-Apart from a-chlorohydrin, compound I1 was one of the most potent inhibitors of ram sperm metabolism; oxidative metabolism was inhibited by 1 .O mM and glycolysis by 0.1 mM (Table 3). This compound also produced infertility in male rats at a concentration equivalent, on a molar basis, to 5 mg of a-chlorohydrin/kg, injected daily for 14 days and it was not toxic at this dose [Brown-Woodman et al, 1976;19791. Compound I1 appears to have potential as a male antifertility agent, but further work is required to determine whether it has any of the toxic side effects of a-chlorohydrin at higher doses.…”

“…This compound inhibited the oxidative metabolism of ram spermatozoa at 10 mM and glycolysis at 1 mM (Table 4). Obviously, the compound is not as active as a-chlorohydrin in suppressing the metabolism of ram spermatozoa in vitro or reducing the fertility of male rats [Brown-Woodman et al, 1976;19791. Compound I V metabolism of ram spermatozoa and 1 .O mM was required for a significant effect ( Table 5). Fructose utilization was reduced at 0.1 mM, but some lactic acid still accumulated at this concentration, presumably because its oxidation was not suppressed as much as with achlorohydrin.…”

Fibrous sheath of mammalian spermatozoa

“…These analogs are metabolized to (S)-3-chlorolactaldehyde, a competitive substrate inhibitor of GAPD activity in mammalian sperm (Stevenson and Jones, 1985). They caused dose-dependent inhibition of sperm glycolysis and motility at concentrations that did not inhibit GAPD activity in other tissues (Brown-Woodman et al, 1978;Brown-Woodman and White, 1976;Ford and Harrison, 1983). These studies provide additional evidence that glycolysis is necessary for sperm motility and fertilization, and further suggest that GAPDS serves a pivotal role in this process.…”