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Biomedical subjects

I G White

Publications and source records attributed to I G White.

At least 37 records · Page 2Linked to original sources
PubMed1986

Mechanism of inhibition of fructolysis in ram spermatozoa by chlorinated antifertility agents.

When ejaculated ram spermatozoa were incubated with (S)-alpha-chlorohydrin (up to 0.25 mM) the oxidative metabolism of fructose to carbon dioxide was inhibited in a concentration-dependent manner. This appears to be due to inhibition of glyceraldehyde-3-phosphate dehydrogenase which leads to the accumulation of fructose-1,6-bisphosphate, dihydroxyacetone phosphate and, to a lesser extent, glyceraldehyde-3-phosphate. (R)-alpha-Chlorohydrin (10 mM) had no significant effect on the oxidative metabolism of fructose. The inhibition of the oxidative metabolism of fructose by (S)-alpha-chlorohydrin (0.1 mM) was not immediate but was detected after incubation for 15 min. By contrast, (R,S)-3-chlorolactaldehyde (5 mM) caused an immediate inhibition of this metabolic pathway. 1-Chloro-3-hydroxyacetone (0.5 mM) immediately decreased the oxidative metabolism of fructose which resulted in the accumulation of key fructolytic intermediates in a manner comparable to that produced by (S)-alpha-chlorohydrin. At a concentration of 20 mM, 6-chloro-6-deoxyglucose had no significant effect on the metabolic activity of ram spermatozoa. We suggest that the anti-fructolytic actions of (S)-alpha-chlorohydrin and 1-chloro-3-hydroxyacetone are mediated via a common metabolite, (S)-3-chlorolactaldehyde, and that the inactivity of 6-chloro-6-deoxyglucose is due to the inability of ram spermatozoa to metabolise this chlorinated sugar to (S)-3-chlorolactaldehyde.

Acetone↗
PubMed1986

Antifertility activity and toxicity of alpha-chlorohydrin aromatic ketal analogues in male rats.

The antifertility activity and toxicity of alpha-chlorohydrin and seven aromatic ketal derivatives were investigated in male rats. At a dose of 5 mg/kg injected intraperitoneally each day for 14 days, alpha-chlorohydrin and the methoxy benzaldehyde derivative (compound 2) produced complete infertility. The benzaldehyde derivative (compound 1) was 89% effective and the other five compounds 71-25% effective. All compounds except the least effective antifertility agent, the methylbenzaldehyde derivative (compound 3), reduced the motility of sperm recovered from the epididymis. None of the compounds caused a decrease in body or testes weight but some increased adrenal weight.

Animals↗
PubMed1986

ATP-induced reactivation of ram testicular, cauda epididymal, and ejaculated spermatozoa extracted with Triton X-100.

It was possible to demembrante and reactivate not only freshly collected testicular, cauda epididymal, and ejaculated ram sperm but also sperm that had been stored for several days at 0 degrees C and for several months at -196 degrees C in rete testis fluid or egg yolk citrate media. Sperm were usually washed free of seminal plasma before demembranation, but this was not essential for reactivation. Bovine serum albumin (1.0%) in the wash medium increased the survival of sperm, but more than 0.25% in the extraction medium decreased reactivation. A macro-molecular component of cauda epididymal fluid also inhibited the reactivation of testicular sperm. Triton X-100 concentrations between 0.01% and 1.00% in the extraction medium were satisfactory for demembranating the sperm. Rapid cooling (i.e., cold shock) mimicked the effect of detergent in making the sperm responsive to added ATP and demonstrated that damage to ram sperm in cold shock does not involve the axoneme. Ejaculated and cauda sperm were reactivated immediately on addition of ATP and activity persisted for up to 10 min. Testicular sperm, on the other hand, required about 4 min to become fully reactivated. The optimal ATP concentration for activation of sperm was 0.1-1.0 mM. Magnesium ions (0.1-1.0 mM) were important for reactivation, and testicular sperm required a higher magnesium concentration than did cauda or ejaculated sperm. Manganese ions were almost as effective as magnesium for reactivating cauda epididymal and ejaculated sperm. Cobalt and cadmium ions were much less active for cauda and ejaculated sperm and none of these ions were effective for testicular sperm. Fluoride (25-50 mM) inhibited reactivation. The presence of 50 microM cAMP in the extraction medium or preincubation of testicular sperm with theophylline or caffeine increased low levels of activation, but this was not evident with ejaculated or cauda sperm. We conclude that the motor apparatus is already functionally assembled in spermatozoa on leaving the testis, but some fine adjustment must take place during maturation in the epididymis.

Adenosine Triphosphate↗
PubMed1985

Effects of malonic, maleic, citric and caffeic acids on the motility of human sperm and penetration of cervical mucus.

The spermicidal effect of four organic acids (malonic, maleic, citric and caffeic acids) was evaluated by adding the acids to sperm, and by observing sperm survival and penetration following addition of these acids to human cervical mucus. Direct addition of 0.1% malonic, maleic and citric acid rendered the sperm immotile by a reduction of pH. In capillaries filled with cervical mucus, the incorporation of 0.01% maleic, malonic and citric acids was sufficient to reduce sperm penetration, and at 0.1%, penetration was completely abolished. Thus, malonic, and maleic and citric acids show promise as cervical or vaginal contraceptives. Caffeic acid was found to be unsuitable owing to its insolubility in aqueous media. Electron microscopy indicated that human sperm do not undergo the acrosome reaction while penetrating cervical mucus in vitro.

Caffeic Acids↗
PubMed1984

Post-thawing survival of motile ram sperm after isolation by layering on protein columns.

Post-thawing survival of ram sperm was examined after semen which had been layered on top of isolation columns containing solutions of bovine serum albumin (BSA) in Tris diluent was processed for freezing by the pellet method. Sperm isolated from the bottom of the BSA column had better post-thawing survival than sperm from the top of the column. The efficiency of sperm isolation was affected by the concentration of BSA in the column, the holding time of semen on the column and the concentration of sperm in the layered semen. The best post-thawing survival of sperm occurred when semen diluted to a concentration of 200 x 10(6) sperm/ml was layered on a column of 6% BSA in Tris diluent and the bottom layer of the column was isolated for freezing after two hours' holding time.

Journal Article↗
PubMed1984

The effect of a single sauna exposure on spermatozoa.

Semen was collected at weekly intervals for 3 wk before and 10 wk after the sauna exposure at 85 degrees C for 20 minutes. The numbers, morphology, ultrastructure, motility, viability and metabolism of the sperm was assessed. Sperm numbers fell within one wk and slowly returned to normal in 5 wk. The earliest ultrastructural change was swelling of the plasma membrane, followed by an increase in the number of immature forms and disorganization of the arrangement of the mitochondria. Motility, glucose utilization and lactic acid accumulation of the sperm rose temporarily immediately after sauna.

Glucose↗
PubMed1982

Calcium ionophore A23187 as a probe for freeze-fracture studies of membrane changes in the head of human spermatozoa.

The membranes of the head of human spermatozoa were examined after incubating the sperm with and without inophore A23187 and calcium ions, using freeze-fracture electron microscopy. After exposure to ionophore and calcium there was a remarkable rearrangement of the intramembraneous particles, especially in the plasma membrane. Buckling of the plasma membrane occurred prior to breaking away from the outer region of the sperm head. The outer acrosomal membrane bubbled and broke down to form vesicles, and blebbing of the inner acrosome membrane also occurred. The nuclear envelope degenerated and often displayed an undulating topography.

Acrosome↗
PubMed1982

Heavy metals and human spermatozoa: II. The effect of seminal plasma on the toxicity of copper metal for spermatozoa.

The ability of copper metal to immobilize human spermatozoa was assessed in vitro. Copper (200 mm2) significantly decreased the percentage of progressively motile spermatozoa over a 3-hour incubation at 37 degrees C. The toxicity of the copper was potentiated by washing the spermatozoa free of seminal plasma. Once they had been immobilized, spermatozoa did not regain motility even after extensive washing, prolonged dialysis, or treatment with copper-specific chelating agents. Apparently copper induces a change in the properties of the spermatozoa which results in irreversible immobilization. The relevance of these observations to the action of intrauterine devices (IUD) bearing copper is discussed.

Copper↗
PubMed1981

Induction of acrosomal reaction in sperm with ionophore A23187 and calcium.

The acrosome reaction was induced in ram, rabbit, and human sperm by incubating with the ionophore A23187 plus calcium ions, although the percentage of reacted sperm was different for each species: 90% in ram, 38% in rabbit, and 69% in man. Fusion of the outer acrosomal and plasma membranes of ram and rabbit sperm formed vesicles, but in human sperm only the outer acrosomal membrane was involved in vesiculation. Acrosin was lost from ram, rabbit, and human sperm after treatment with ionophore plus calcium. Ionophore alone induced the reaction in only 35% of ram sperm, 20% of human sperm, and 12% of rabbit sperm. On exposure to A23187 alone, the acrosome of unreacted rabbit sperm bulged and the acrosome and nuclear membrane of human sperm were often lifted away from the nucleus. The percentage of mammalian sperm undergoing the acrosome reaction in the presence of calcium alone, was very low.

Acrosin↗
PubMed1980

Heavy metals and spermatozoa. 1. Inhibition of the motility and metabolism of spermatozoa by metals related to copper.

The toxicity to human spermatozoa of seven metals (nickel, palladium, platinum, silver, gold, zinc, and cadmium) and one alloy (brass: 80% copper, 20% zinc) related to copper was assessed in vitro. Only brass and cadmium significantly reduced the percentage of motile unwashed spermatozoa; however, washing the spermatozoa increased the spermicidal effectiveness of both brass and cadmium and also resulted in a significant reduction in motility caused by zinc and silver. Oxygen consumption by once-washed spermatozoa was apparently increased by zinc and brass, but the high rate of oxidation of these metals confounds interpretation of their effect. Silver caused a decline in the oxygen uptake of spermatozoa. Silver, zinc, brass, and, to a lesser extent, cadmium decreased the quantity of glucose utilized by spermatozoa and also decreased the glucose oxidized. Accumulation of lactate by washed spermatozoa was impaired severely by zinc and less severely by brass and cadmium.

Adult↗
PubMed1980

Evidence that phospholipid protects ram spermatozoa from cold shock at a plasma membrane site.

Adding phospholipid dispersions to washed ram spermatozoa provided immediate protection against cold shock as judged by the effect on motility. Re-washing the spermatozoa free of dispersed lipid rendered then susceptible to cold shock. Analysis of the spermatozoa showed that exogenous phospholipid had not become interpolated into the cell membranes. The ratio of phospholipid to cholesterol in the spermatozoon was not changed when dispersed phospholipid was added and stayed the same during incubation for 3 h at 37 degrees C. It is concluded that the protective effect of phospholipid against cold shock in ram spermatozoa is due to a 'loose' interaction of the lipid structures with the plasma membrane of the cells.

Animals↗
PubMed1980

Origin of glycerylphosphorylcholine, inositol, N-acetylaminosugar, and prostaglandins in human seminal plasma and their effects on sperm metabolism.

The origin of glycerylphosphorylcholine (GPC), N-acetylaminosugar, inositol, and prostaglandins in human seminal plasma was investigated by correlating the concentration of these components in split ejaculates with known marker constituents. Fructose and acid phosphatase were selected as markers of the secretory activity of the seminal vesicles and prostate gland, respectively, and spermatozoa indicated epididymal origin. The concentration of fructose was lowest in the first fraction of the semen and increased to a maximum in the final portion. Prostaglandins E and F and N-acetylaminosugar values closely followed this pattern, indicating that these components originate in the seminal vesicles. The concentration of spermatozoa was high in the first two fractions, decreasing to a minimum in the final fraction. The distribution of GPC was similar to that of the spermatozoa, indicating that the epididymis secretes this compound. Inositol levels were similar in all fractions, indicating that it is probably present in epididymal, vesicular, and prostatic fluid. Human spermatozoa were unable to utilize N-acetylglucosamine or inositol. High concentrations of some prostaglandins (100 micrograms/ml of PGF1 alpha, 15S 15 met. F2 alpha, PGA1, and PGA2) depressed the endogenous oxygen uptake of human spermatozoa.

Acetylglucosamine↗
PubMed1980

Evaluation of ten potential organic spermicides.

The following compounds, selected as possible vaginal or cervical spermicides, were tested in vitro for their ability to decrease the motility of human spermatozoa: cytochalasins A and B, N-cetylpyridinium chloride (CPC), N-cetyl-N,N,N-trimethylammonium bromide (CTAB), sodium deoxycholate (SDC), quinine and emetine hydrochlorides, 4-nitrophenyl-4-guanidinobenzoate hydrochloride, n-hexanal, and 6-amidino-2-(4-amidinophenyl) dilactate. The most effective spermicide was the antibacterial cytochalasin A which instantaneously abolished motility at a concentration of 0.01%. The two cationic detergents CPC and CTAB were also very potent and instantly immobilised spermatozoa at a concentration of 0.1%. Quinine, emetine and 4-nitrophenyl-4-guanidinobenzoate hydrochlorides at a concentration of 0.1% abolished motility in 30-60 minutes. n-Hexanal, SDC, and the antihaemostatic compound 6-amidino-2-(4-amidinophenyl) dilactate at 0.1% depressed motility but never rendered the sperm completely immotile. Cytochalasin B had little or no effect on sperm motility even at 0.1%.

Cetrimonium Compounds↗
PubMed1979

The antifertility activity and toxicity of alpha-chlorohydrin derivatives in male rats.

The antifertility activity and toxicity of alpha-chlorohydrin, six derivatives and glycidol were investigated in male rats. At a dose of 5 mg/kg injected intraperitoneally each day for 14 days, only alpha-chlorohydrin produced complete infertility. When rats were injected with the derivatives at a dose equivalent to 5 mg/kg of alpha-chlorohydrin on a molar basis, the phosphorylated and amino acid derivatives produced complete infertility within 7 days; however, there were some signs of toxicity. Compound II also produced complete infertility and appeared less toxic. AY - 22,352, compounds III and IV and glycidol had no antifertility activity, although spermatozoan motility was reduced by injection of glycidol.

Adrenal Glands↗
PubMed1978

Mode of action of alpha-chlorohydrin as a male anti-fertility agent. Inhibition of the metabolism of ram spermatozoa by alpha-chlorohydrin and location of block in glycolysis.

1. The effect of alpha-chlorohydrin on the metabolism of glycolytic and tricarboxylate-cycle substrates by ram spermatozoa was investigated. The utilization and oxidation of fructose and triose phosphate were much more sensitive to inhibition by alpha-chlorohydrin (0.1-1.0mm) than lactate or pyruvate. Inhibition of glycolysis by alpha-chlorohydrin is concluded to be between triose phosphate and pyruvate formation. Oxidation of glycerol was not as severely inhibited as that of the triose phosphate. This unexpected finding can be explained in terms of competition between glycerol and alpha-chlorohydrin. A second, much less sensitive site, of alpha-chlorohydrin inhibition appears to be associated with production of acetyl-CoA from exogenous and endogenous fatty acids. 2. Measurement of the glycolytic intermediates after incubation of spermatozoal suspensions with 15mm-fructose in the presence of 3mm-alpha-chlorohydrin showed a ;block' in the conversion of glyceraldehyde 3-phosphate into 3-phosphoglycerate. alpha-Chlorohydrin also caused conversion of most of the ATP in spermatozoa into AMP. After incubation with 3mm-alpha-chlorohydrin, glyceraldehyde 3-phosphate dehydrogenase and triose phosphate isomerase activities were decreased by approx. 90% and 80% respectively, and in some experiments aldolase was also inhibited. Other glycolytic enzymes were not affected by a low concentration (0.3mm) of alpha-chlorohydrin. Loss of motility of spermatozoa paralleled the decrease in glyceraldehyde 3-phosphate dehydrogenase activity. alpha-Chlorohydrin, however, did not inhibit glyceraldehyde 3-phosphate dehydrogenase or triose phosphate isomerase in sonicated enzyme preparations when added to the assay cuvette. 3. Measurement of intermediates and glycolytic enzymes in ejaculated spermatozoa before, during and after injection of rams with alpha-chlorohydrin (25mg/kg body wt.) confirmed a severe block in glycolysis in vivo at the site of triose phosphate conversion into 3-phosphoglycerate within 24h of the first injection. Glyceraldehyde 3-phosphate dehydrogenase activity was no longer detectable and both aldolase and triose phosphate isomerase were severely inhibited. Spermatozoal ATP decreased by 92% at this time, being quantitatively converted into AMP. At 1 month after injection of alpha-chlorohydrin glycolytic intermediate concentrations returned to normal in the spermatozoa but ATP was still only 38% of the pre-injection concentration. Motility of spermatozoa was, however, as good as during the pre-injection period. The activity of the inhibited enzymes also returned to normal during the recovery period and 26 days after injection were close to pre-injection values. 4. An unknown metabolic product of alpha-chlorohydrin is suggested to inhibit glyceraldehyde 3-phosphate dehydrogenase and triose phosphate isomerase of spermatozoa. This results in a lower ATP content, motility and fertility of the spermatozoa. Glycidol was shown not to be an active intermediate of alpha-chlorohydrin in vitro.

Animals↗