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

Ford, W. C. L.; Waites, G. M. H.

doi:10.1530/jrf.0.0520153

Cited by 37 publications

(11 citation statements)

References 6 publications

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“…Each series of incubations included flasks which were acidified at zero time. Subsequent manipulations and the collection of 14C02 were carried out as described previously (Ford & Waites, 1978). Motility was scored as the percentage of spermatozoa which were progressively motile and was assessed subjectively with a phase-contrast microscope (x400 magnification).…”

Section: Incubationsmentioning

confidence: 99%

The role of oxidative phosphorylation in the generation of ATP in human spermatozoa

Ford¹,

Harrison²

1981

Reproduction

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Washed human spermatozoa had an endogenous oxygen uptake of 2.14 +/- 0.17 nmol O2/10(8) spermatozoa/min (mean +/- s.e..m., n = 35) which was stimulated by succinate (Vmax = 9.64 +/- 0.44 nmol O2/10(8) spermatozoa/min) but not by other substrates. The ATP concentration in freshly washed spermatozoa was 12.18 +/- 0.54 (s.e.m.) nmol/10(8) spermatozoa (n = 26) and was maintained for 2 h in the presence of 2 mM-D-glucose but fell to 9.56 +/- 0.73 (s.e.m.) nmol/10(8) spermatozoa (n = 13) in its absence. The presence of 2 microM-antimycin A, 2 microM-rotenone, 0.4 microM-carbonyl cyanide m-chlorophenyl hydrazone or 8 microM-oligomycin caused the ATP concentration to fall to less than 2 nmol/10(8) spermatozoa but their effect was partly alleviated by 2 mM-glucose. Sodium malonate (5 mM) prevented the stimulation of respiration by succinate but had no effect on the ATP concentration of the spermatozoa or their ability to produce 14CO2 from [U-14C]glucose. The least active of the tricarboxylic acid cycle enzymes was 2-oxoglutarate dehydrogenase (EC 1.2.4.2) (3.1 +/- 0.6 (s.e.m.) nmol substrate transformed/10(8) spermatozoa/h (n = 4). Cytochrome c oxidase (EC 1.9.3.1) was much less active than in rat spermatozoa (22.3 +/- 6.0 (s.e.m., n = 4) and 615 +/- 87 (n = 4) nmol transformed/10(8) spermatozoa/min). It is concluded that human spermatozoa can obtain ATP by the respiration of endogenous substrate but the substrates and metabolic pathways involved remain obscure.

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Section: Incubationsmentioning

confidence: 99%

The role of oxidative phosphorylation in the generation of ATP in human spermatozoa

Ford¹,

Harrison²

1981

Reproduction

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“…There is good evidence therefore that the glycolytic effect in sperm is closely linked to antifertility activity. With this in mind we decided to investigate the effect of chlorodeoxy sugars on male fertility and sperm glycolysis, in the hope that these compounds might either inhibit the glycolytic pathway in spermatozoa themselves or be broken down to a n active intermediate in the body (Ford & Waites 1978).…”

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confidence: 99%

Chlorinated Sugars: A Biochemical Approach to the Control of Male Fertility

Ford

Waites

1978

Int J of Andrology

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6‐Chloro‐6‐deoxyglucose (120 μmol; 24 mg kg b.wt.), 6‐chloro‐6‐deoxyfructose (< 240 μ 48 mg/kg b.wt.), 6‐chloro‐6‐deoxysucrose (240 μmol; 85 mg/kg b.wt.), ′6‐chloro‐′6‐deoxysucrose (< 240 μmol; 85 mg/kg b.wt.) and 6.′6‐dichloro‐6,′6‐dideoxysucrose (240 μmol; 89 mg/kg b.wt.) administered to male rats daily, by oral gavage, render them infertile after 7 days treatment. The effect is sustained through at least 4 weeks of treatment and is reversed 3 to 6 weeks after treatment is withdrawn. Spermatozoa from the cauda epididymidis of treated rats oxidize only 10% as much glucose as spermatozoa from controls and their ATP and total adenine nucleotide content fall more rapidly during incubation with 2 mM [U14C]D‐glucose. These biochemical effects are associated with a more rapid decline in cell motility. The LD50 for 6‐chloro‐6‐deoxyglucose in the rat is > 16 g/kg b.wt. Administration of [36Cl] ′6‐chloro‐′6‐deoxysucrose has shown this compound to be extensively dechlorinated in vivo. Chlorodeoxy sugars are discussed as potential male antifertility agents worthy of further investigation.

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“…Several 6-chloro-6-deoxysugars have an antifertility action in the male rat (Ford & Waites, 1978a, b, 1980Heitfeld, McRae & Vickery, 1979;Ford, 1980) and 6-chloro-6-deoxyglucose is also effective in the male marmoset monkey (J. P. Hearn, unpublished data). Their effect is similar to that of a-chlorohydrin (Jones, 1978) and it is believed that they act by preventing the metabolism of glucose by spermatozoa from treated animals.…”

Section: Introductionmentioning

confidence: 96%

Effects of 6-chloro-6-deoxysugars on glucose oxidation in rat spermatozoa

Ford¹,

Harrison²,

Waites³

1981

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Summary. 6-Chloro-6-deoxyfructose or 6-chloro-6-deoxyglucitol (>90 \g=m\mol/kg/ day), 6-chloro-6-deoxyglucose or 6-chloro-6-deoxymannose (>120 \g=m\mol/kg/day) and 6-chloro-6-deoxygalactose (>300 \g=m\mol/kg/day) all had an antifertility action in the male rat when given by mouth. Spermatozoa from the infertile rats were unable to oxidize glucose. This effect was always produced by a lower dose than the antifertility effect and the threshold dose for the 2 effects varied in a parallel fashion between the different 6-chloro-6-deoxysugars. Glucose oxidation appeared to be inhibited at the triose phosphate isomerase or glyceraldehyde 3-phosphate dehydrogenase reaction. These effects of 6-chloro-6-deoxysugars are similar to those of \g=a\-chlorohydrin.The activities of the glycolytic enzymes were greatly in excess of the observed flux through the pathway and high concentrations of glucose 6-phosphate and triose phosphate accumulated in rat spermatozoa incubated with 2 mM-D-glucose.

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

Cited by 37 publications

References 6 publications

The role of oxidative phosphorylation in the generation of ATP in human spermatozoa

The role of oxidative phosphorylation in the generation of ATP in human spermatozoa

Chlorinated Sugars: A Biochemical Approach to the Control of Male Fertility

Effects of 6-chloro-6-deoxysugars on glucose oxidation in rat spermatozoa

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