Effects of the optical isomers of  -chlorohydrin on glycolysis by ram testicular spermatozoa and the fertility of male rats

Abstract

When 0-1 mM-S alpha-chlorohydrin was present in incubations, glycolysis by ram testicular spermatozoa was almost completely inhibited whereas 10 mM-R alpha-chlorohydrin had no effect. Male rats dosed orally with S alpha-chlorohydrin (3-25 mg/kg/day) became much less fertile than controls but those dosed with R alpha-chlorohydrin (13 mg/kg/day) did not. The loss of fertility was associated with a reduced ability of spermatozoa from the cauda epididymidis of these rats to oxidize glucose. It is concluded that the S enantiomer is responsible for both the inhibition of sperm glycolysis and the reduction in fertility caused by the racemic mixture of alpha-chlorohydrin.

A reversible contraceptive action of some 6-chloro-6-deoxy sugars in the male rat

“…Blood was collected from the heart immediately after death and glucose was measured by the hexokinase pro¬ cedure (Bergemeyer, 1974). Spermatozoa were expelled from the cauda epididymidis by retrograde flushing (Ford et al, 1977) and pooled within each group. They were dispersed in phosphatebuffered saline (100 mM-NaCl, 3 mM-KCl, 6-5 mM-Na2HP03,1-5 mM-KH2P04, 0-8 mM-CaCl2 and 0-5 mM-MgCl2) (PBS) (Edwards et al, 1976) containing 90 µg penicillin G and 120 µg streptomycin sulphate/ml.…”

“…The antifertility action of low doses of -chlorohydrin (3-chloropropan-l,2-diol) on the male (Ericsson & Youngdale, 1970) is associated with a marked reduction in the ability of spermatozoa from treated animals to oxidize glucose (Mohri, Suter, Brown-Woodman, White & Ridley, 1975;Edwards, Dacheux & Waites, 1976;Ford, Harrison & Waites, 1977) and it is possible that this may be the primary cause of the antifertility action. With the glycolytic effect in mind, we have examined the action of some chlorinated sugars on the fertility of male rats.…”

The interaction of -chlorohydrin with glycerol kinase

“…The demonstration that the antifertility effect of -chlorohydrin is specific to the S(+)isomer (Jackson & Robinson, 1976;Ford, Harrison & Waites, 1977;Jackson, Rooney & Fitzpatrick, 1977) is comparable with the differential antifertility action of the isomers of l,amino-3,chloro-2-propanol (Paul, Williams & Cohen, 1974;Coppola & Saldarmi, 1974) …”

In Vitro Evaluation of Acrosomal Status and Motility in Rat Epididymal Spermatozoa Treated with .ALPHA.-Chlorohydrin for Predicting Their Fertilizing Capacity.

“…P rev io us inv es ti gati on s repo r ted t hat α -chlorohydrin has direct effects on mature sperm [23 ], in hi bi t s g ly ce ra ld eh yd e-3 -ph o s ph at e dehydrogenase, which forms part of the glycolytic pathway, and eventually causes spermatozoa to lose energy [13][14][15]. A (S)-α-chlorohydrin, a racemate of α-chlorohydrin, is metabolized by spermatozoa to (S)-3-chlorolactealdehyde by an enzyme that is involved in the oxidation of glycerol to glyceraldehyde [25].…”

“…These actions are dose dependent and can be classified as the lowdose effect and the high-dose effect [11,12]. The low-dose effect is noted in mature sperm contained in the cauda epididymis and vas deferens without visible morphologic changes, and is known to inhibit the glycolytic pathway [13][14][15]. When the movement of spermatozoa from male rats treated with α-chlorohydrin was analyzed with a computer assisted sperm analysis (CASA) system, swimming velocity was reduced with or without a decrease in the percentage of motile sperm [16,17].…”