Effect of  -chlorohydrin on glucose metabolism by spermatozoa from the cauda epididymidis of the rhesus monkey (Macaca mulatta)

Abstract

Summary. Spermatozoa from the cauda epididymidis of the rhesus monkey had metabolic properties similar to those published for ejaculated spermatozoa. The concentration of glycolytic intermediates was low until 2 mM-glucose was added; glucose 6-phosphate, fructose 1,6-bis-phosphate and the triose phosphates then increased but glycerate 3-phosphate did not. It was concluded that the activity of glyceraldehyde 3-phosphate dehydrogenase (EC 1.2.1.12) limited flux through the glycolytic pathway. The production of lactate and CO2 from glucose was strongly inhibited in the presence of 5 or 10 mM-\g=a\-chlorohydrin. The energy charge of the spermatozoa was low before and after 1 h incubation with 2 mM-glucose (0\m=.\5\ m=+-\ 0\m=.\05and 0\m=.\05\m=+-\0\m=.\06 respectively) and the value after the incubation was decreased in the presence of 5 or 10 mM-\g=a\-chlorohydrin (0\m=.\17\ m=+-\0\m=.\05and 0\m=.\15\m=+-\0\m=.\04 respectively). \g=a\-chlorohydrin inhibited glycolysis at the glyceraldehyde 3-phosphate dehydrogenase reaction.

Inhibition of Fructolysis in Boar Spermatozoa by the Male Antifertility Agent (S)-a-Chlorohydrin

“…Similar effects have been observed when ram and rhesus monkey spermatozoa were incubated with (R,S)-cx-chlorohydrin (Brown-Woodman et al 1978;Ford and Harrison 1980) but the present study is' the first to demonstrate that it is the (S)-isomer that is effective and that the (R)-isomer is devoid of any inhibitory activity. Furthermore, the degree of inhibition observed on ram and rhesus monkey spermatozoa was not as marked indicating that boar spermatozoa are more susceptible to the inhibitory action of (S)-cx-chlorohydrin than are those from the other species.…”

“…Inhibition by (R,S)-cx-chlorohydrin of the oxidation of fructose or glucose to COz by rat, ram, boar, rhesus monkey and human spermatozoa in vitro has been well established (Hommonai et al 1975;Brown-Woodman et al 1978;Ford et al 1979;Ford and Harrison 1980;Hutton et al 1980). In the present study, this inhibitory effect on the metabolism of boar spermatozoa has been shown to be confined to the (S)-isomer of cx-chlorohydrin.…”

“…This is confirmed by the decrease in the energy charge potential of boar spermatozoa when they are incubated in the presence of (S)-cx-chlorohydrin. For example, at a concentration of O· 5 mM, the (S)-isomer reduced the energy charge potential to 34% of control values in 1 h. By contrast, the energy charge potential of rhesus monkey spermatozoa was effected in a similar manner in the same period of time but only in the presence of 5 mM (R,S)-cx-chlorohydrin (Ford and Harrison 1980), which is five times the effective concentration of the (S)-isomer on boar spermatozoa. It seems, therefore, that mature spermatozoa of those species susceptible to the action of cx-chlorohydrin are rendered non-functional because they cannot utilize fructose, their major source of energy for the production of ATP (BrownWoodman et al 1975).…”

“…Studies in vitro with mature spermatozoa obtained from the cauda epididymides of the rat, ram, boar and rhesus monkey? and with ejaculated human spermatozoa, have shown that the compound inhibits glycolysis (Homonnai et al 1975;Brown-Woodman et al 1978;Ford et al 1979;Ford and Harrison 1980;Hutton et al 1980). The principle site of this inhibitory action in ram and rhesus monkey spermatozoa is known to involve the glyceraldehydephosphate dehydrogenase (Ee 1.2.1.12) reaction (Brown-Woodman et al 1978;Ford and Harrison 1980).…”

Interference with Epididymal Physiology as Possible Site of Male Contraception

“…Low doses (2.5-10 mg/kg/day) of a-chlorohydrin (3-chloropropan-1,2-diol) induced reversible male infertility in several mammalian species, including rat [16, Cauda epididymal spermatozoa from animals given low doses of a-chlorohydrin break down glucose and fructose less rapidly than the spermatozoa from controls [17,20,311. When spermatozoa from untreated animals are incubated in vitro with low concentrations of a-chlorohydrin (< 1 mM), glycolysis is greatly reduced [15,19,311; this failure is accompanied by a rapid decrease in motility and ATP content of the inhibited cells compared with controls [ l l , 171.…”