Male Antifertility Compounds: Efficacy of U-5897 in Primates (Macacamulatta)

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.

Section: Methodssupporting

confidence: 83%

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

Back¹,

Glover²,

Shenton³

et al. 1975

“…The fact that U-5897 produces temporary or permanent sterility in the male rat, only temporary sterility in the guinea-pig and monkey (Ericsson & Baker, 1970;Kirton et al, 1970) (Mason & Young, 1967). It is suggested that the cadmium ion affects either the testicular vessels and their epididymal branches (Gunn, Gould, & Anderson, 1963), or their end-arterial capillary bed (Mason, Brown, Young & Nesbit, 1964).…”

Section: Discussionmentioning

confidence: 99%

Male Antifertility Compounds: U-5897 as a Rat Chemosterilant

Ericsson¹

1970

Self Cite

107

“…-Chlorohydrin (3-chloropropan-l,2-diol) produces reversible infertility in male animals of several species including the rhesus monkey (Kirton, Ericsson, Ray & Forbes, 1970; Setty, Kar, Roy & Chowdhury, 1970;Jones, A. R., 1978). Glycolysis is inhibited in spermatozoa from treated animals and in spermatozoa from untreated animals exposed to a-chlorohydrin in vitro (Brown-Woodman, Mohri, Mohri, Suter & White, 1978;Ford, Harrison, Takkar & Waites, 1979).…”

Section: Introductionmentioning

confidence: 99%

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

Ford¹,

Harrison²

1980

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.