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B Macé

Publications and source records attributed to B Macé.

At least 19 recordsLinked to original sources
PubMed2006

Chromosome constitution and apoptosis of immature germ cells present in sperm of two 47,XYY infertile males.

BACKGROUND: In order to assess sperm alterations observed in some XYY males, we analysed the chromosome constitution as well as apoptosis expression in germ cells from two oligozoospermic males with high count of immature germ cells in their semen. METHODS: Sex chromosome number and distribution were assessed at pachytene stage by fluorescence in situ hybridization (FISH). Immature germ cells and spermatozoa were examined by FISH and TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end (TUNEL) assay, combined with immunocytochemistry using the proacrosin-specific monoclonal antibody (mAb 4D4). RESULTS: For patients 1 and 2, two Y chromosomes were present in respectively 60.0 and 39.6% of pachytenes. The three sex chromosomes were always in close proximity and partially or totally condensed in a sex body. XYY spermatocytes I escape the pachytene checkpoint and achieve meiosis. Nevertheless, nuclear division and/or cytokinesis were often impaired during meiosis leading to diploid (mainly 47,XYY cells) and tetraploid (94,XXYYYY) meiocytes. The presence of binucleated (23,Y)(24,XY) immature germ cells resulting from cytokinesis failure agree with a preferential segregation of the two Y chromosomes during meiosis I. In addition, 69.6% (patient 1) and 53.12% (patient 2) of post-reductional round germ cells were XY. However, high level of apoptotic round germ cells (94.9% for patient 1 and 93.3% for patient 2) was detected and may explain the moderate increase of hyperhaploid XY spermatozoa. Segregation errors also occurred in the XY cell line responsible for disomic 18 and X, as well as 46,XY diploid spermatozoa. CONCLUSIONS: Our data are in agreement with the persistence of the extra Y chromosome during meiosis in XYY oligozoospermic males responsible for spermatogenesis impairment and a probable elimination via apoptosis of most XYY germ cells not solely during but also after meiosis.

Adult↗
PubMed2005

[Cryopreservation of immature testicular tissue].

An increased incidence of cancer is observed in the population of adolescents and young adults since thirty years. Major progress in cancer diagnosis and therapy is unfortunately associated to high degree of toxicity on gonad function. Cryopreservation of ovarian tissue is performed in girls and women before cancer treatment with high risk of infertility. Procedures for ejaculated or testicular extracted spermatozoa are well defined. However, for prepubertal boys or after ejaculated sperm collection failure, mature or immature testicular tissue banking should be proposed. Still, an optimal cryopreservation protocol is a prerequisite for clinical application and does not exist for the moment. Furthermore, the future applications of immature testicular tissue banking should be developed, not solely germ cell in vitro maturation but also autologous testicular tissue grafting.

Animals↗
PubMed2004

[Chromosome abnormalities of spermatozoa].

Chromosome meiotic pairing during male meiosis is a major event for chromosome segregation during anaphase I and spermatogenesis normal process. Chromosome non-disjunctions responsible for aneuploidy in male gametes can be observed during the first and the second meiotic divisions. The analysis of sperm nuclei chromosome constitution is a major and indirect tool for assessing male meiotic non-disjunctions and the genesis of chromosomal abnormalities. This evaluation has been performed initially by the human sperm/hamster oocyte fusion assay and more recently by fluorescence in situ hybridisation (FISH). Therefore, male populations with increased risk of aneuploidy for their progeny could be identified before entering an in vitro fertilization procedure, and depending on the potential risk a preimplantation or prenatal genetic diagnosis could be performed. For males with constitutional chromosome abnormalities, a specific genetic counselling could also be proposed.

Aneuploidy↗
PubMed2003

Meiotic segregation of sex chromosomes in mosaic and non-mosaic XYY males: case reports and review of the literature.

The aim of this study was to determine the incidence of sex chromosome aneuploidy in spermatozoa of two males with a 47,XYY karyotype and one male with a 46,XY/47,XYY constitution. Spermatozoa obtained from two oligospermic patients and one volunteer semen donor were studied by multicolour fluorescence in situ hybridization. In the XY/XYY male, the frequencies of X-bearing to Y-bearing sperm were significantly different from the 1 : 1 expected ratio. Significantly increased frequencies were found in the mosaic and non-mosaic males for 24,XX and 24,YY sperm when compared with control donors. The number of 24,XY sperm was significantly different from the controls in the XYY males, but not in the mosaic male. The incidence of disomy 18 and the rate of diploidy also increased in the three patients. However, the mosaic male had the lowest cumulative rate of disomic and diploid spermatozoa when compared with the two XYY patients. Our data suggest that: (i) chromosome abnormalities observed in spermatozoa of the two XYY oligoasthenoteratospermic (OAT) males arise through segregation errors in XY germ cells rather than normal meiosis of XYY germ cells, (ii) mosaic XYY males with normal semen parameters have a lower risk of producing offspring with a sex chromosomal abnormality than OAT males with XYY karyotype.

Adult↗
PubMed2000

Assessment of sex chromosome aneuploidy in sperm nuclei from 47,XXY and 46,XY/47,XXY males: comparison with fertile and infertile males with normal karyotype.

Sex chromosome aneuploidy was assessed in spermatozoa from a 47,XXY male and a 46,XY/47,XXY male using three colour fluorescence in-situ hybridization (FISH) and compared with two control groups. The first group included subjects of proven fertility and the second infertile males with normal constitutional karyotype. The frequencies of XX and YY disomic, XY hyperhaploid and diploid spermatozoa were significantly increased in the 47,XXY male compared to subjects from the two control groups (P < 0.0001). For the 46,XY/47,XXY sample, the same results were observed, except that the incidence of YY disomic spermatozoa did not differ significantly from the rate obtained in infertile patients. The frequency of sex chromosome aneuploidy did not differ significantly between the 47,XXY and the 46,XY/47,XXY males, except for XX disomic sperm nuclei which was higher in the 47,XXY patient. The frequency of chromosome 12 disomy was also increased in the two XXY individuals (0.42 and 0.49% respectively; P < 0.0001). The meiotic abnormalities observed in the two XXY patients arose through segregation errors in XY germ cells. The increased number of meiotic non-disjunctions observed in the germ cells of infertile males may be a common feature of the deficient oligo- or azoospermic testis. Patients with Klinefelter's syndrome with oligozoospermia have an increased risk of both sex chromosome and autosome aneuploidy in their progeny.

Adult↗
PubMed1999

Relationship between clinical phenotype, semen parameters and aneuploidy frequency in sperm nuclei of 50 infertile males.

The purpose of this study was to analyse the frequency of disomy for chromosomes 1, 13, 14, 18, 21, 22, X and Y in sperm nuclei of 50 infertile men and 10 healthy probands of proven fertility. Semen parameters (sperm count, global motility and morphology), urological clinical examination, genital ultrasound and lymphocyte karyotyping were performed for each patient. Disomy frequency was established by fluorescence in situ hybridization by using whole chromosome paint probes. The mean rate of disomy for the various autosomes studied was higher in infertile males than in subjects of proven fertility. Interchromosomal and interindividual differences in the disomy frequency were observed between the 50 patients. The mean frequency of homodisomy YY and heterodisomy XY was increased in spermatozoa of patients with low semen quality parameters (0.24% and 0.54%, respectively). The disomy frequency in infertile males was directly correlated with the severity of oligospermia. However, no relationship was established between aneuploidy rate, sperm motility, morphology or clinical phenotype. These results support the hypothesis that, during spermatogenesis of males with sperm parameter alterations, a decreased frequency of meiotic chromosome pairing and crossing over may lead to spermatogenesis arrest at the meiosis stage and/or to an increase of meiotic nondisjunctions. Meiotic arrest in some germ cells may be responsible for oligospermia and nondisjunctions in other cells for aneuploidy in mature male gametes.

Adult↗
PubMed1998

Assessment of autosome and gonosome disomy in human sperm nuclei by chromosome painting.

Disomy and diploidy frequencies for autosomes 1-22 and the gonosomes were assessed in 299,442 sperm nuclei from four normal fertile men by chromosome painting. This novel approach allowed us to perform a specific and sensitive detection of each chromosome. A minimum of 5000 sperm nuclei per subject were evaluated for each chromosome by dual colour fluorescence in situ hybridization. The disomy rate proved to be similar for all the autosomes (0.24%) and the diploidy rate varied from 0.12% to 0.15%. No interchromosomal or interindividual differences in the frequency of disomic and diploid sperm nuclei were observed between the four subjects. The mean frequency of XX-, YY- and XY-bearing spermatozoa was estimated to 0.17%, 0.17% and 0.32%, respectively. This strategy constitutes a new approach for detecting aneuploidy in human sperm nuclei and suggests an equal repartition of non-disjunction among chromosomes in male gametes.

Adult↗
PubMed1998

Full-term delivery following intracytoplasmic sperm injection with frozen-thawed immotile testicular spermatozoa.

We present one of the very few deliveries occurring following intracytoplasmic sperm injection of thawed immotile testicular spermatozoa from a testicular biopsy of a man with bilateral congenital absence of the vas deferens. A first attempt in the 33 year old woman with fresh testicular biopsy extracted spermatozoa was unsuccessful. The supernumerary spermatozoa were cryopreserved for later use. After thawing, testicular spermatozoa were immotile. From 11 intact oocytes injected with frozen-thawed immotile testicular spermatozoa, a two pronuclear fertilization rate of 27% and a cleavage rate of 100% were obtained. A total of three embryos was transferred resulting in a singleton pregnancy and the birth of a normal female baby.

Adult↗
PubMed1997

Role of endogenous endothelin in chronic heart failure: effect of long-term treatment with an endothelin antagonist on survival, hemodynamics, and cardiac remodeling.

BACKGROUND: Plasma levels of the vasoconstrictor peptide endothelin (ET) are increased in chronic heart failure (CHF), and ET levels are a major predictor of mortality in this disease. Thus, ET may play a deleterious role in CHF. The purpose of this study was to assess the effects of chronic treatment with the ET receptor antagonist bosentan in a rat model of CHF. METHODS AND RESULTS: Rats were subjected to coronary artery ligation and were treated for 2 or 9 months with placebo or bosentan (30 or 100 mg x kg(-1) x d(-1)). Bosentan 100 mg x kg(-1) markedly increased survival (after 9 months: untreated, 47%; bosentan, 65%; P<.01). Throughout the 9-month treatment period, bosentan significantly reduced arterial pressure and heart rate. After 2 or 9 months of treatment, the ET antagonist reduced central venous pressure and left ventricular (LV) end-diastolic pressure as well as plasma catecholamines, urinary cGMP, and LV ventricular collagen density. Bosentan also reduced LV dilatation (evidenced at 2 months by a shift in the pressure/volume relationship ex vivo). Echocardiographic studies performed after 2 months showed that the ET antagonist reduced hypertrophy and increased contractility of the noninfarcted LV wall. The lower dose of bosentan (30 mg x kg(-1)), which had no major hemodynamic or structural effects, also had no effect on survival. CONCLUSIONS: Long-term treatment with an ET antagonist markedly increases survival in this rat model of CHF. This increase in survival is associated with decreases in both preload and afterload and an increase in cardiac output as well as decreased LV hypertrophy, LV dilatation, and cardiac fibrosis. Thus, chronic treatment with ET antagonists such as bosentan might be beneficial in human CHF and might increase long-term survival in this disease.

Animals↗
PubMed1997

Early versus delayed angiotensin-converting enzyme inhibition in experimental chronic heart failure. Effects on survival, hemodynamics, and cardiovascular remodeling.

BACKGROUND: The efficacy of ACE inhibitors in congestive heart failure (CHF) might be affected by the pathophysiological status present at the onset of treatment. We compared in a rat model the effects of ACE inhibition (lisinopril, 10 mg.kg-1.d-1) initiated early (1 week) or late (3 months) after myocardial infarction (i.e., at time points corresponding to moderate or severe CHF without or with established cardiac remodeling). METHODS AND RESULTS: Survival was improved by early treatment at 3 months (from 76% to 95%) and by both early and delayed treatment at 9 months (placebo, 28%; early, 90%; delayed, 61%). Delayed treatment was initiated in a more severe pathophysiological context of CHF than early treatment, illustrated in untreated rats by higher left ventricular (LV) end-diastolic and central venous pressures and by increased LV weight and LV cavity circumference. After 9 months, early and delayed treatments reduced systolic, LV end-diastolic, and central venous pressures. Both treatments also similarly decreased LV weight, LV cavity circumference, and LV collagen density. CONCLUSIONS: In this rat model of CHF, early and delayed ACE inhibitor treatments both increase survival and exert similar beneficial effects on cardiac hemodynamics and remodeling. Although early treatment prevents the development of ventricular dysfunction and remodeling, delayed treatment is capable of reversing cardiac hypertrophy and remodeling, as well as ventricular dysfunction. Thus, ACE inhibitors exert marked beneficial effects even when treatment is initiated late into the evolution of heart failure (ie, at a time of established ventricular dysfunction and remodeling).

Analysis of Variance↗
PubMed1997

Increased survival after long-term treatment with mibefradil, a selective T-channel calcium antagonist, in heart failure.

OBJECTIVES: We sought to investigate the effects of mibefradil on survival, hemodynamic variables and cardiac remodeling in a rat model of chronic heart failure (HF) and to compare these effects with those of the angiotensin-converting enzyme (ACE) inhibitor cilazapril. BACKGROUND: The use of calcium channel blocking agents in chronic HF has been disappointing. Most studies have shown that these drugs have either no or even detrimental effects due in part to the negative inotropic effects they induce. Mibefradil is a calcium channel blocker that selectively blocks T channels and displays moderately negative inotropic properties only at high doses. Because T channels are upregulated in the hypertrophied heart and could mediate hypertrophic signals and increase arrhythmogenicity, blockade of these channels might be beneficial in chronic HF. METHODS: Rats were subjected to coronary artery ligation and 9 months of treatment with mibefradil (15 mg/kg body weight per day) or cilazapril (10 mg/kg per day) or no treatment. Survival and systolic blood pressure were assessed over the 9-month treatment period, after which cardiac hemodynamic variables and structure were determined. RESULTS: Mibefradil increased survival rate to the same extent as cilazapril (71% for mibefradil vs. 75% for cilazapril and 44% for no treatment). Mibefradil decreased systolic blood pressure, although to a lesser extent than cilazapril. Both treatments decreased left ventricular (LV) end-diastolic and central venous pressures, without any change in the first derivative of LV pressure over time or heart rate. Mibefradil decreased LV weight (although less than cilazapril) without affecting right ventricular weight. Finally, both drugs normalized LV collagen density. CONCLUSIONS: Mibefradil in a rat model improved survival to the same extent as an ACE inhibitor, without impairing LV function, and was associated with a reduction in LV weight and fibrosis. Thus, mibefradil might be beneficial in the treatment of chronic HF.

Animals↗
PubMed1997

Response of large and small vessels to alpha and beta adrenoceptor stimulation in heart failure: effect of angiotensin converting enzyme inhibition.

The increased sympathetic drive in chronic heart failure (CHF) might provoke vascular adrenoceptor desensitization, which, together with endothelial dysfunction, could contribute to the altered vasomotor tone seen in CHF. We investigated 1) whether CHF alters the responses mediated by alpha and beta adrenoceptors in small and large peripheral arteries, and 2) the effect of angiotensin-converting enzyme (ACE) inhibition. Rats with CHF (coronary artery ligation) were treated with placebo or the ACE inhibitor lisinopril (10 mg/kg/d) starting 7 days after ligation. Responses to phenylephrine (alpha 1 agonist), salbutamol (beta 2 agonist) as well as acetylcholine (endothelium-dependent), were assessed after 3 months in isolated and pressurized segments of the abdominal aorta, the femoral and the mesenteric arteries. In animals with hemodynamic signs of CHF, neither the vasoconstrictor responses to phenylephrine nor the vasodilator response to salbutamol were affected. In contrast, the dilator response to acetylcholine of both small arteries, but not that of the aorta, was impaired. Furthermore, CHF did not modify vessel structure. While lisinopril did not modify the responses to adrenergic agonists, it normalized the response to acetylcholine. Furthermore, ACE inhibition reduced vascular media cross sectional area and collagen density. Thus, the unchanged arterial responsiveness to adrenoceptor agonists does not indicate any vascular adrenoceptor desensitization, while endothelial dependent vasodilation of small arteries is impaired in CHF. ACE inhibition does not modify the response to adrenergic stimuli, prevents endothelial dysfunction and induces both cardiac and vascular remodeling, which probably contribute to the effect ACE inhibitors have on exercise tolerance and survival.

Acetylcholine↗
PubMed1996

Peripheral artery structure and endothelial function in heart failure: effect of ACE inhibition.

Chronic heart failure (CHF) induces peripheral vasoconstriction and impairs endothelium-dependent relaxation of large arteries. We investigated in a rat model of CHF (coronary artery ligation) 1) whether endothelial dysfunction also exists in resistance arteries, 2) whether this is associated with vascular morphological changes, and 3) the effect of angiotensin-converting enzyme (ACE) inhibition on these parameters. After 1 mo or 1 yr, CHF reduced the vasodilatory response to acetylcholine of isolated, perfused femoral and mesenteric artery segments. This impairment was more marked in femoral than in mesenteric arteries. However, CHF did not induce any arterial remodeling. Chronic treatment with the ACE inhibitor perindopril improved the response to acetylcholine and reduced media cross-sectional area and collagen density. Thus at the level of small peripheral arteries, CHF induces an endothelial dysfunction but does not affect vascular structure. ACE inhibition prevents the CHF-induced endothelial dysfunction and induces vascular remodeling. These changes could contribute to the observed beneficial effects of ACE inhibitors on hemodynamics and survival in CHF.

Acetylcholine↗
PubMed1995

Vascular and myocardial protective effects of converting enzyme inhibition in experimental heart failure.

Systemic vasoconstriction due to stimulation of the sympathetic and renin-angiotensin-aldosterone systems is a hallmark of heart failure and this is accompanied by impaired endothelium-dependent relaxations at the level of large arteries. This study investigated, in a rat model of heart failure, whether such an endothelial dysfunction also exists at the level of the resistance artery, and whether this is associated with morphologic changes, as well as the effects of chronic treatment with the angiotensin-converting enzyme inhibitor perindopril (2 mg/kg/day). After 12 months, arterial pressure, left ventricular (LV) end diastolic pressure (LVEDP), and LV dP/dt were measured in anesthetized rats. Responses to acetylcholine and nitroprusside were determined in isolated and perfused mesenteric artery segments (diameter: 280 +/- 15 microns). After fixation, vessel diameter, media cross-sectional area, and media collagen and elastin densities were measured by image analysis. After 12 months, untreated rats showed signs of heart failure, i.e., reduced LV dP/dt, and increased LVEDP, heart weight/body weight, LV cavity circumference, and myocardial collagen density. In mesenteric vessels the endothelium-dependent vasodilator response to acetylcholine was impaired, whereas the response to the nitric oxide donor nitroprusside was unaffected. Heart failure did not affect vascular morphological parameters. Perindopril decreased blood pressure and LVEDP without any modification of LV dP/dt, and prevented cardiac remodeling. At the vascular level, perindopril improved the response to acetylcholine and reduced media cross-sectional area and collagen density without affecting internal vessel diameter or elastin density. Thus, heart failure decreases endothelium-dependent vasodilator response to acetylcholine without modification of vessel structure.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1984

Chromatin structure and nucleic acid synthesis in human lymphocyte activation by phytohemagglutinin.

Alterations in chromatin structure were explored as a function of time following phytohemagglutinin (PHA) activation of human lymphocytes. Nuclear refringency (related to chromatin status), ultrastructural changes, and modifications of nucleic acid synthesis were compared. Chromatin dispersion was observed within 20 min of stimulation, with a concomitant increase in [3H]uridine incorporation; both were inhibited by actinomycin D. Recondensation of chromatin had occurred at 60 min when RNA synthesis was still increasing. The early chromatin dispersion thus was a reversible step and one of the most striking cellular events during the first phase of PHA activation. Late chromatin dispersion of blastic cells during the second phase of PHA response (after 24 h) was related to DNA synthesis in mitotic cells. This step was also inhibited by actinomycin D. These results suggest a relationship between the morphological changes in chromatin structure and the induction of RNA and DNA syntheses. The regulation of transcriptional and replicational states of the nucleus is discussed in terms of modifications of chromatin structure, considering PHA-induced calcium and cyclic nucleotide metabolism and interleukin II receptor expression.

Adult↗
PubMed1984

Kinetics of the histological changes in lymphoid organs and of the T-cell inducing capacity of serum in mice treated with Imuthiol (sodium diethyldithiocarbamate).

Sodium diethyldithiocarbamate ( Imuthiol ) triggers in mice an increased production of T-cell recruiting factors and an early and prolonged hyperplasia in the T-cell dependent areas of peripheral lymphoid organs, partially independent from thymus modification. The data confirm previous findings on the role of an extrathymic factor and are consonant with the notion of a feedback regulation to control T-cell differentiation.

Animals↗