The control of male fertility by 6-chloro-6-deoxysugars

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

doi:10.1051/rnd:19800618

Cited by 18 publications

(10 citation statements)

References 11 publications

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“…The emphasis of these investigations was on the site of attack of at-chlorohydrin, especially on the metabolism of sperm [32,33]. To date, the only available data on changes in epididymal proteins caused by (x-chlorohydrin and 6-chloro-6-deoxyglucose, a metabolite also inhibiting the activity of glyceraldehyde 3-phosphate dehydrogenase in rats in a manner similar to achlorohydrin [34,35], are from Tsang et al [36], who investigated the effect on epididymal protein secretion and the acquisition of sperm surface proteins by D gel electrophoresis. They found that protein patterns of cauda epididymidal fluids from treated animals were similar to those from control animals, but there were some quantitative changes concerning iodination of sperm surface proteins.…”

Section: Discussionmentioning

confidence: 98%

Shedding of a Rat Epididymal Sperm Protein Associated with Infertility Induced by Ornidazole and α-Chlorohydrin1

Wagenfeld¹,

Yeung²,

Strupat

et al. 1998

Biology of Reproduction

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The protein composition of epididymal fluid and sperm extracts of rats treated with the nitroimidazole compound ornidazole was investigated by two-dimensional gel electrophoresis. Epididymal luminal fluid from the corpus and cauda regions of male animals rendered infertile by ornidazole treatment contained a prominent protein (contraception-associated protein 1, CAP1) with a molecular mass of approximately 25 kDa and an isoelectric point (pI) of 5.8; it was not found in fluids, but was present in sperm, from fertile vehicle-fed rats. Infrared matrix-assisted laser desorption/ionization mass spectrometry indicated that the molecular mass of CAP1 was 20420+/-120 daltons. Analysis of 17 amino acids demonstrated 49% homology to a diuretic hormone from an insect (Acheta domesticus). Densitometric quantitation of CAP1 on silver-stained gels indicated its presence in greater amounts in cauda than in corpus fluid from treated animals, whereas fluid from the rete testis lacked CAP1. In vitro incubations of tissue from the caput, corpus, and cauda epididymidal regions with [35S]methionine gave no hint that CAP1 was a secretion product of the epididymal epithelium. The absence of CAP1 from luminal fluid obtained from the sperm-depleted corpus epididymidis of efferent duct-ligated ornidazole-fed rats suggested a spermatozoal origin. CAP1 was present in spermatozoa from the caput epididymidis but not from the rete testis in control animals. Less CAP1 was present in detergent extracts of cauda sperm from ornidazole-treated rats than in sperm from control animals, suggesting a contraceptive-related displacement of protein from sperm to fluid. The association of ornidazole- and alpha-chlorohydrin-induced infertility with the presence of CAP1 in epididymal fluid, probably originating from spermatozoa, suggests a critical role for this protein in fertilization.

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Section: Discussionmentioning

confidence: 98%

Shedding of a Rat Epididymal Sperm Protein Associated with Infertility Induced by Ornidazole and α-Chlorohydrin1

Wagenfeld¹,

Yeung²,

Strupat

et al. 1998

Biology of Reproduction

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“…This is probably because we included 0-1% Triton X-100 in the extraction media but did not include a low speed centrifugation step before assaying the homogenates. The activities given by Brooks (1977) would not be adequate to explain the rate of respiration by rat epididymal spermatozoa in the presence of added substrates (Ford & Waites, 1980). Sodium arsenite was expected to inhibit both pyruvate dehydrogenase (EC 1.2.4.1) and 2-oxoglutarate dehydrogenase (Webb, 1966) and its effect was specific since it did not significantly decrease the production of lactate from glucose or the ability of the spermatozoa to obtain ATP from this process.…”

Section: Discussionmentioning

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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“…However, high doses of -chlorohydrin are required to inhibit the oxidation of acetate, pyruvate or lactate by ram spermatozoa (Brown-Woodman et al, 1978). Moreover, spermatozoa from rats treated with 6-chloro-6-deoxyglucose (24 mg/kg/day), which has an antifertility effect similar to that of -chlorohydrin (Ford & Waites, 1978), can remain motile and retain a high energy charge when supplied with 2 mM-pyruvate plus 4 mM-DL-lactate as substrates although these parameters decline rapidly when 2 mM-glucose is the only substrate given (Ford & Waites, 1980). Therefore, unless spermatozoa are compelled to metabolize sugar at some stage, e.g.…”

Section: Discussionmentioning

confidence: 99%

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

Ford¹,

Harrison²

1980

Reproduction

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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.

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The control of male fertility by 6-chloro-6-deoxysugars

Cited by 18 publications

References 11 publications

Shedding of a Rat Epididymal Sperm Protein Associated with Infertility Induced by Ornidazole and α-Chlorohydrin1

Shedding of a Rat Epididymal Sperm Protein Associated with Infertility Induced by Ornidazole and α-Chlorohydrin1

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

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

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