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Biomedical subjects

C Gagnon

Publications and source records attributed to C Gagnon.

At least 199 records · Page 11Linked to original sources
PubMedDate not supplied

Origin of a motility inhibitor within the male reproductive tract.

Seminal plasma contains a motility inhibitor of demembranated reactivated spermatozoa. We investigated its origin within the reproductive tract. The highest level of inhibitor was detected in seminal vesicle fluids from the three species investigated (bull, rat, rabbit). Significant levels of inhibitor were also observed in prostatic fluids. Testes and epididymal fluids, as well as bulbo-urethral and coagulating gland homogenates were essentially devoid of inhibitor. On a mg protein basis, the inhibitor in seminal vesicle fluid was about four times less active than the inhibitor of seminal plasma. The high level of inhibitor in seminal plasma can not be explained by the synergistic effect of the combination of seminal vesicle, prostatic and epididymal fluids. Dialysis experiments suggested that the high level of inhibitor in seminal plasma was mainly due to the presence of a dialysable activator. This activator is capable of potentiating up to four-fold the inhibitor present in seminal vesicle fluid.

Adenosine Triphosphate↗
PubMedDate not supplied

The presence of a motility inhibitor within spermatozoa may explain the poor sperm motility of some infertile men.

The presence of motility inhibitors in seminal plasma and within spermatozoa from control and infertile men with poor sperm motility was investigated using demembranated reactivated human spermatozoa. No difference was found in the inhibitory capacities in seminal plasma of patients with poor sperm motility (less than 50%) when compared with that of fertile controls with motility above 50%. No correlation was observed between inhibitory capacity and sperm motility. However, when extracts of spermatozoa from these patients were tested for the presence of inhibitor, it was observed that three of nine patients had an inhibitor in their sperm extract. By contrast, all sperm extracts from fertile control subjects were devoid of inhibitor. It was concluded that the presence of a motility inhibitor in seminal plasma does not explain the poor sperm motility observed in patients. The presence of a motility inhibitor within spermatozoa, however, may represent an important factor in the etiology of the poor sperm motility observed in some patients.

Adult↗
PubMedDate not supplied

Nitrocellulose and polyvinyl coatings prevent sperm adhesion to glass without affecting the motility of intact and demembranated human spermatozoa.

The effectiveness of several glass coating agents in preventing sperm adherence to glass surfaces for both intact and demembranated human spermatozoa was investigated. These agents included bovine serum albumin (BSA), Sigmacote, poly glu-lys, Collodion and Formvar. The presence of at least 5% of seminal plasma in sperm suspensions prevented sperm adhesion to glass surfaces. On the other hand, 56% of washed spermatozoa resuspended in an isoosmotic buffer containing 1 mg/ml of BSA attached to glass. Collodion, Formvar and Sigmacote reduced sperm attachment to glass to 2, 5 and 7%, respectively. BSA was partially effective, with 20% sperm adherence to glass, and poly glu-lys was totally ineffective. Whereas Sigmacote and BSA coatings lacked transparency, Collodion always achieved the best light transmission. Demembranated reactivated spermatozoa were all attached to glass within 90 seconds of contact. This adhesion was prevented by Collodion and Formvar. Other agents were less effective or interfered with motility. In contrast to intact spermatozoa, demembranated spermatozoa have a very low progressiveness ratio (vector speed/track speed), a wide beating amplitude and because of their whiplash flagellar movement, their motility resembles that of hamster capacitated spermatozoa.

Cell Adhesion↗
PubMedDate not supplied

Purification and characterization of a sperm motility inhibitor in human seminal plasma.

A sperm motility inhibitor from human seminal plasma was purified and characterized. The purification procedure includes dialysis, ion exchange chromatography on SP-Sephadex C-25 and adsorption chromatography on hydroxylapatite. With this procedure, the seminal plasma motility inhibitor was purified 290-fold with a 24% recovery in inhibitory activity. Its molecular weight has been estimated at 18,000 to 22,000 by sodium dodecyl sulfate polyacrylamide gel electrophoresis, but at 13,000 to 15,000 according to molecular sieving under native conditions. The mobility inhibitor has an isoelectric point pH 9.1. It is stable over a wide range of pH (5 to 10) and at temperatures up to 60 C. The observation that the seminal plasma factor inhibited purified bull dynein ATPase in a concentration-dependent manner may suggest that it blocks the motility of demembranated spermatozoa by interfering with dynein arm function.

Adenosine Triphosphatases↗
PubMedDate not supplied

Comparing women's assessment of midwifery and medical care in Québec, Canada.

In 1990, the province of Québec, Canada, adopted a law that authorized the evaluation of the practice of midwifery through pilot projects before its legalization. A key objective of this evaluation, as defined by the law, was the documentation of women's assessment of maternity care, especially with regard to humanization and continuity of care. Two to 3 months after birth, 933 midwifery clients and 1,000 physicians' clients, matched on several characteristics, responded to a mailed questionnaire (response rates were 93% and 76%, respectively). Results showed that women from both groups were generally satisfied with the care they received, although women who received midwifery care were assessed as more positive on every issue surveyed. Objective measures supported impressions that were also confirmed through qualitative data analysis: midwifery clients had a greater number of and longer prenatal visits, their care was perceived to be more personalized, and a greater number of midwives' clients breastfed their infants. However, the interpretation of these results must take into account that the two groups had different personal expectations and values with regard to health and health care. These findings are enlightening in evaluating women's needs, expectations, and satisfaction with health care services and should be included in future development of maternity care, including idwifery services, in Québec and other locations.

Cohort Studies↗
PubMedDate not supplied

Grafts in the treatment of Parkinson's disease: animal models.

Long-term treatment of parkinsonian patients with L-DOPA leads to a loss of efficacy over time and the appearance of important side effects such as dyskinesias. Grafts of chromaffin cells of the adrenal medulla or fetal ventral mesencephalic neurons bring behavioral improvement in animal models of Parkinson's disease. These improvements are likely to be related to the secretion of dopamine by the grafted cells and/or to the reinnervation of the host tissue. In addition, a leak in the blood-brain barrier may allow peripheral catecholamines to gain access to the brain. Lack of clear effects of grafts in parkinsonian patients may be due to their poor survival in the human brain. Improvement of grafting techniques as well as the addition of neurotrophic factors to grafts may help increase their survival and improve behavioral effects. Recently, genetic techniques have allowed the creation of genetically modified cell lines which can produce L-DOPA and these cells may be grafted in the brain. Interestingly, these cell lines may be encapsulated in permselective membranes which can protect them from immunological rejection and avoid the uncontrolled cell growth of these mitotically active cells. Grafting techniques seem to be an interesting alternative to treat parkinsonian patients. Improvement of grafting procedures may help increase survival of grafts and thus enhance behavioral improvements. Moreover, genetic modification of well-known tumor cell lines or patient's own cells such as astrocytes may help avoid the low availability as well as ethical and immunological problems linked to the use of fetal human tissue.

Adrenal Medulla↗
PubMedDate not supplied

The cyclic GMP-specific phosphodiesterase inhibitor, sildenafil, stimulates human sperm motility and capacitation but not acrosome reaction.

Capacitation is the series of transformations that spermatozoa undergo in the female genital tract in order to bind to the zona pellucida, initiate the acrosome reaction, and fertilize an egg. Cyclic adenosine monophosphate (cAMP) plays an important role in this process and its levels are regulated by 2 key enzymes, adenylyl cyclase and cyclic nucleotide phosphodiesterase (PDE), the latter being involved in cAMP degradation. Evidence was provided for the involvement of PDE in sperm motility and capacitation. Of the 10 gene families of PDE that exist in mammalian tissues, the calcium-calmodulin-dependent (type 1) and the cAMP-specific (type 4) have been found in human spermatozoa. Using sildenafil, we investigated a highly potent cyclic guanosine monophosphate (cGMP)-specific PDE (type 5) inhibitor and whether this PDE is present in human spermatozoa and is involved in sperm functions. Sildenafil inhibited PDE activity of Percoll-washed spermatozoa with an IC50 of 97+/-3 and 33+/-3 microM when cAMP and cGMP, respectively, were used as substrates. Because the IC50 of sildenafil obtained for PDE type 5 is much lower (2 to 6 nM) than that obtained with sperm PDE, the data suggest that PDE type 5 represents only a small fraction of the whole PDE activity of spermatozoa. Sildenafil causes dose-dependent increases in sperm cAMP levels and capacitation, which are associated with an increase in the levels of tyrosine phosphorylation of 2 fibrous sheath proteins (p105/81). Sperm velocity, amplitude of lateral head displacement, and hyperactivation were increased at 30-180 minutes. Sildenafil did not trigger the acrosome reaction in capacitated spermatozoa. These results suggest that under our experimental conditions, sildenafil triggers human sperm motility and capacitation, probably via its inhibitory action on PDE activity other than type 5 with a resultant rise in cAMP levels.

1-Methyl-3-isobutylxanthine↗
PubMedDate not supplied

Semenogelin, the main protein of semen coagulum, inhibits human sperm capacitation by interfering with the superoxide anion generated during this process.

Semenogelin (Sg), the major protein of the human semen coagulum, is present at high concentrations in seminal vesicle secretions. It is degraded by the prostate-specific antigen (PSA) to generate peptides of various biological activities that were found on and inside spermatozoa. Our aim was to determine the effect of Sg on capacitation, which is the series of transformations that spermatozoa must undergo to become fertile. At concentrations of 0.1 to 1.0 mg/mL (600- to 20-fold lower than those of semen), Sg did not affect sperm motility (%) but completely prevented capacitation induced by fetal cord serum ultrafiltrate; a partial inhibition of capacitation was noted with 0.03 mg Sg/mL. There was also a dose-dependent decrease in the tyrosine phosphorylation of fibrous sheath proteins and in the O2-.-related chemiluminescence. Ribonuclease (RNase), which has as high an isoelectric point (pI = 9.7) as Sg (pI = 9.5), also prevented sperm capacitation and O2-.-related chemiluminescence but to a lower extent, suggesting that one mechanism of Sg action on spermatozoa could be related to its positive charge at physiological pH. Sg at 1, but not 0.3 or 0.1 mg/mL, scavenged the O2-. generated by the mix of xanthine + xanthine oxidase and modified the kinetics of the reaction; RNase did not have such effects. Therefore, Sg is a potential scavenger for O2-. but probably also affects the sperm oxidase. Spermatozoa rapidly processed Sg; a high proportion of Sg was degraded after 15 minutes of incubation. The resulting polypeptide patterns were reminiscent of those obtained with PSA as a proteolytic enzyme. These data suggest that Sg, its degradation products, or both may be natural regulators of sperm capacitation and could prevent this process from occurring prematurely. One mechanism by which Sg acts could involve an interference with the O2-. that is normally generated during this process.

Humans↗
PubMedDate not supplied

Reactive oxygen species and human spermatozoa. I. Effects on the motility of intact spermatozoa and on sperm axonemes.

Mammalian spermatozoa are sensitive to oxygen-induced damages mediated by lipid peroxidation of the cell membrane. The aim of this study was to evaluate whether reactive oxygen species (ROS) could also induce axonemal damage. When Percoll-separated spermatozoa were treated with hydrogen peroxide, or the combination xanthine and xanthine oxidase (X + XO), there was a progressive decrease, leading to a complete arrest, in sperm flagellar beat frequency. Once demembranated in a medium containing magnesium adenosine triphosphate (Mg.ATP), ROS-immobilized spermatozoa still reactivated motility; however, the percentage and duration of motility obtained in these tests gradually decreased to zero in the next hour. In 50% of the cases, motility of intact spermatozoa spontaneously reinitiated after 6 to 24 hours of immobilization due to ROS treatment, although with percentages and beat frequencies lower than those of untreated spermatozoa. Studies using ROS scavengers (such as catalase, superoxide dismutase, and dimethylsulfoxide) indicated that hydrogen peroxide was the most toxic of the ROS involved, but that .O2- and .OH probably also played a role in immobilization of spermatozoa by ROS. The data suggest that ROS induce a chain of events leading to sperm immobilization, that axonemes are affected, and that limited endogenous repair mechanisms exist to reverse these damages.

Adult↗
PubMedDate not supplied

Reactive oxygen species and human spermatozoa. II. Depletion of adenosine triphosphate plays an important role in the inhibition of sperm motility.

Under moderate conditions, reactive oxygen species (ROS) have been shown to inhibit sperm motility after several hours of incubation. The rapid decrease in flagellar beat frequency observed within the first hour of contact between ROS and spermatozoa was associated with a rapid loss of intracellular adenosine triphosphate (ATP). Motility of intact spermatozoa ceased when their ATP concentration was reduced by 85 +/- 5%. Axonemal damage was confirmed when ROS-treated spermatozoa could not reactivate motility after demembranation in a medium containing magnesium adenosine triphosphate (Mg.ATP). However, in conditions allowing rephosphorylation of the axonemes (addition of cyclic adenosine monophosphate, or cAMP, and protein kinase or sperm extracts to the demembranation medium), the motility could reactivate. Three lines of evidence suggested that ATP depletion induced by ROS treatment was responsible for the effects observed in spermatozoa. First, the rapid decrease in intracellular ATP observed after ROS treatment was closely followed by a decrease in beat frequency, loss of intact sperm motility, and axonemal damage due to insufficient phosphorylation. Second, incubation of spermatozoa with the combination pyruvate-lactate allowed maintenance of sperm ATP at a normal level and prevented the effects of ROS; furthermore, spermatozoa immobilized after ROS treatment, then supplemented with pyruvate-lactate, were able to reinitiate motility in parallel with an increase in their ATP level. Third, treatment of spermatozoa with rotenone, an ATP depleting agent, produced effects similar to ROS treatment and could also be reversed by the addition of pyruvate-lactate. These data are consistent with the conclusion that ROS treatment produced axonemal damage mostly as a result of ATP depletion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMedDate not supplied

Hyperactivated motility is coupled with interdependent modifications at axonemal and cytosolic levels in human spermatozoa.

Whether the motility characteristics of hyperactivated spermatozoa were determined by stable changes at the axonemal level and whether the presence of cytosolic factors was required for the expression of these changes was investigated. Different degrees of sperm hyperactivation were produced in Percoll-washed spermatozoa after incubation for 1 hour to 3 hours at 37 degrees C in Ham's F-10 supplemented with human blood plasma or fetal cord serum. Decomplemented fetal cord serum induced the highest percentage of hyperactivation (19 +/- 3%), followed by human plasma (13 +/- 2%). Fetal cord serum that was not decomplemented did not induce a level of hyperactivation (1.7 +/- 0.2%) significantly different from control levels (0.9 +/- 0.2%). Dialyzed fetal cord serum induced intermediate levels of hyperactivation (6 +/- 1%). The motility characteristics of demembranated sperm models of hyperactivated spermatozoa induced by decomplemented fetal cord serum and nonhyperactivated spermatozoa were compared by videomicroscopy and computer-assisted digital image analysis. After demembranation with Triton X-100 and reactivation of motility by Mg. adenosine triphosphate (Mg.ATP), hyperactivated and nonhyperactivated spermatozoa showed similar motility characteristics. However, hyperactivated spermatozoa that were demembranated and reactivated in cytosolic extracts from hyperactivated spermatozoa had significantly higher (P less than 0.05) linear velocity (33 +/- 4 mu/sec) and lower linearity (0.23 +/- 0.04) than control spermatozoa that were demembranated and reactivated in control cytosolic extracts (velocity = 24 +/- 1 mu/sec; linearity = 0.32 +/- 0.02). The data suggest that the expression of hyperactivated motility requires interdependent changes at the axonemal and cytosolic levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMedDate not supplied

Low levels of nitric oxide promote human sperm capacitation in vitro.

The influence of nitric oxide on human sperm hyperactivation and capacitation, as well as its mechanism of action and its possible origin from spermatozoa were studied. Percoll-washed spermatozoa from healthy volunteers were incubated in Ham's F-10 medium supplemented or not with the nitric oxide-releasing agents, diethylamine-NONOate or spermine-NONOate, in combination or not with superoxide dismutase or catalase (scavengers for the superoxide anion and for hydrogen peroxide, respectively), or with sodium nitrate, sodium nitrite, or preincubated NONOates. Sperm hyperactivation, capacitation, and nitric oxide synthase activity were determined. High concentrations (0.3 to 1 mM) of NONOates reduced sperm motility. However, a lower concentration (0.1 mM) of the two NONOates had no effect on the percentage of sperm motility or of hyperactivation but resulted in a significant increase in sperm capacitation (24% +/- 4%) when compared to that of control spermatozoa (Ham's F-10 alone, 12% +/- 2%). Nitric oxide released by the NONOates appeared responsible for this effect because sodium nitrate or nitrite or preincubated NONOates (to exhaust the formation of nitric oxide) had no influence on sperm capacitation. Catalase, but not superoxide dismutase, abolished the capacitating action of the NONOates. No nitric oxide synthase activity was detected in spermatozoa, whether they were in their basal state or already capacitated. Furthermore, the nitric oxide synthetase inhibitor L-NG nitroarginine methyl ester did not block sperm capacitation induced by fetal cord serum ultrafiltrate. It is therefore concluded that, although spermatozoa do not possess detectable nitric oxide synthase activity, low levels of nitric oxide induce human sperm capacitation, and this action likely involves hydrogen peroxide.

Acrosome↗
PubMedDate not supplied

Effect of sperm lipid peroxidation on fertilization.

This study was aimed at determining, with homologous mouse gametes, whether a level of membrane lipid peroxidation insufficient to affect sperm motility parameters can alter sperm fertilizing potential. The addition of ferrous ions and ascorbic acid (Fe2+/ Asc) to mouse sperm suspensions increases the formation of thiobarbituric acid-reactive substances (TBARS), an indicator of lipid peroxide breakdown products, without significantly affecting the level of sulfhydryl groups. In the presence of Fe2+/Asc concentrations above > 0.4/2.0 mM, spermatozoa become immotile. However, at concentrations < or = 0.4/2.0 mM of Fe2+/Asc, i.e., conditions in which the TBARS formation is increased by < or = 4.6-fold over that of controls, motility remains unaffected for up to 3 hours. In the presence of 0.4/ 2.0 mM Fe2+/Asc, treated spermatozoa increase their fertilizing potential by 50%, as measured by the formation of two-cell embryos. This increase is not caused by improvements in sperm motility parameters (percentage, linearity, velocity, hyperactivation) or sperm capacitation. On the other hand, there is a significant increase in the capacity of mouse spermatozoa to bind to homologous zona pellucida. In conclusion, mild peroxidative conditions, that increase lipid peroxide formation 4.6-fold without significantly modifying free sulfhydryl groups and sperm motility parameters, improve the fertilizing potential of spermatozoa by increasing their binding capacity to zona pellucida.

Animals↗