The Effects of  -Chlorohydrin on the Composition of Rat and Rabbit Epididymal Plasma: A Possible Explanation of Species Difference

Abstract

Summary. The relationship between the antifertility effect of \g=a\-chlorohydrin and changes in composition of luminal plasma from the cauda epididymidis of rats and rabbits has been investigated.At each dose regimen studied, the fertilizing capacity of rats treated with \g=a\-chlorohydrin was reduced to zero. The levels of sodium, potassium, glycerylphosphorylcholine (GPC), acid phosphatase and alkaline phosphatase in epididymal plasma were not markedly affected by drug treatment. The most noticeable change was a considerable increase in the concentration of lactic dehydrogenase (LDH) at all dose levels and of glutamic-oxaloacetic transaminase (GOT) after 7 days of treatment with 8 and 16 mg/kg. The effect of cold shock on the composition of epididymal plasma showed that LDH and GOT are, at least in part, derived from spermatozoa.In contrast, \g=a\-chlorohydrin did not have an antifertility action in the rabbit, and the only notable change in the composition of epididymal plasma was an increase in the level of GPC.These results provide evidence that, in the rat, \g=a\-chlorohydrin or a metabolite primarily exerts its antifertility effect by a direct action on the spermatozoa, whilst in the rabbit a barrier may exist to the entrance of the drug into the lumen of the epididymal duct.

Antifertility Actions of a-Chlorohydrin in the Male

“…Attempts to exploit this physiological effect and cause negative population growth by the 'sterile male approach' have been effective in isolated rat colonies (Anderson 1977). Acceptance by wild rats of baits containing a-chlorohydrin has been successful and the compound is now marketed as a rodenticide in many countries under the name Epibloc* (Anon. 1982;Ericsson 1982), a use which, incidentally, was suggested nearly 40 years ago (Leffingwell and Lesser 1945).…”

“…When (R,S)-oc-[ 36 C1]ch10rohydrin was incubated with rabbit sperm, there was neither an inhibition of fructo1ysis nor the production of 3-ch10ro1acta1dehyde (Jones et al 1981). Since oc-ch10rohydrin is ineffective as an antifertility agent when administered to male rabbits (Back et al 1975), this indicated that species specificity may be due to the ability of mature sperm to produce (S)-3-ch10ro1acta1dehyde. Furthermore, isolated kidney tubules from the rabbit, rat and the boar were incapable of performing this biotransformation and their glycolytic activity was unimpaired in the presence of oc-ch10rohydrin (Jones et al 1981).…”

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

“…The antifertility action of IX-chlorohydrin in vitro is species-specific. While affecting male fertility in a number of species, there is no activity in either the rabbit or the mouse (Ericsson 1970;Back et al 1975). If an antifertility response requires the formation of (R)-3-chlorolactaldehyde within mature spermatozoa, it may be that the spermatozoa of these two species are incapable of carrying out the necessary biotransformation.…”