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.     

Evolution des caractères spermatiques avec l’âge

The increasing life expectancy and the increasingly advanced age of parenthood due to socio-economic conditions in developed countries, combined with progress in medically-assisted procreation techniques account for the recent interest in the fertility of ageing men. Hormonal changes (primary testicular deficiency, decreased amplitude of hypothalamic GnRH secretion peaks), morphological and histological testicular changes (arteriolar sclerosis, Leydig cell and Sertoli cell degeneration, rarefaction of germ cells, thickening of the testicular tunica albuginea) related to physiological ageing are relatively well documented. The repercussions of these physiological changes on the quality of the semen of ageing men is difficult to clearly establish because of the limited data available and the marked interindividual variability of semen parameters. Globally, the quality of semen gradually decreases with age, although a cut-off age cannot be defined. The alterations observed essentially concern the volume of the ejaculate, and the mobility and morphology of spermatozoa. The sperm count appears to be less markedly affected. However, all of the other pathological and psychosocial factors frequently observed in ageing men must be taken into account in the interpretation of the data (changes of the bladder neck and genital tract, chronic diseases, drug treatments, smoking, decreased frequency of sexual intercourse, partner’s age). Further comparative studies, including a larger number of elderly patients in clearly defined age-groups, with populations matched for other risk factors for alteration of semen quality, are necessary. Overall, a review of the literature does not reveal any specific prognostic criteria for age-related fertility. Regardless of the semen characteristics of an ageing man desiring possible paternity, a complete clinical and andrological assessment must be performed.     

A review of curcumin as a biological stain and as a self-visualizing pharmaceutical agent

Curcumin has been widely used to color textiles but, unlike other natural dyes such as hematoxylin or saffron, it rarely has been discussed as a biological stain. Aspects of the physicochemistry of curcumin relevant to biological staining and self-visualization, i.e., its acidic properties, lipophilicity, metal and pseudometal complexes, and optical properties, are summarized briefly here. Reports of staining of non-living biological specimens in sections and smears, both fixed and unfixed, including specimens embedded in resin, are summarized here. Staining of amyloid, boron and chromatin are outlined and possible reaction mechanisms discussed. Use of curcumin as a vital stain also is described, both in cultured monolayers and in whole organisms. Staining mechanisms are considered especially for the selective uptake of curcumin into cancer cells. Staining with curcumin labeled nanoparticles is discussed. Toxicity and safety issues associated with the dye also are presented.     

Cultural transmission of fitness: genes take the fast lane

Classical population genetics describes how the fate of an allele is driven by four forces: mutation, migration, selection and drift. However, these are sometimes insufficient to explain how the observed allele frequency changes and, therefore, another factor must be invoked: cultural transmission of fitness (CTF). CTF is the non-genetic transmission of any kind of behaviour that affects reproductive success. There are several clearly documented examples of CTF, and theoretical studies have shown that it affects effective population size, linkage disequilibrium and coalescent times. It is therefore a factor that must be taken into account to explain the structure of genetic diversity. In this article, we will present documented cases of how CTF affects the genetic diversity of populations and yields dramatic changes in allele frequencies.     

Wright-Fisher revisited: the case of fertility correlation

We study the non-genetic inheritance of fertility from parents to offspring. For this purpose, we propose an exchangeable extension of the Wright-Fisher model. This extension allows us to introduce non-genetic fertility correlation in the forward in time process and to study its effects on the genealogies of individuals (or genes) samples. Since it is independent of the gene considered, this effect is uniform on the genome, even in diploid populations. For values of fertility correlation observed in human populations, we show that coalescence times are strongly but inhomogenously reduced and that the shape of gene genealogies is markedly unbalanced. Despite the fact that our simulations concern stationary populations, the former non-genetic effect is very similar to what has been described for populations of variable size such as populations passing through demographic bottleneck. However, additional strong tree imbalance due to non-genetic causes is reported here for the first time.     

Immune factors influencing the course of infection with Neospora caninum in the murine host

This paper investigates the role of specific immune factors on the course of infection in genetic knockout (gko) mice infected with 3 different strains of Neospora caninum. Survival time and parasite persistence were examined in interferon-gamma (IFN-gamma), tumor necrosis factor receptor-2 (TNFR2), interleukin 10 (IL-10), beta 2 microglobulin (beta2M), and inducible nitric oxide synthase (iNOS2) gko or wild-type (wt) mice following infection with either pathogenic (NC-1 or NC-2) or attenuated (NCts-8) N. caninum strains. Infection with NC-1 was 100% lethal in IFN-gamma gko mice, as evidenced by mean survival times of 10-13 days, depending on the challenge dose used. TNFR2 and beta2M gko mice infected with NC-1 or NC-2 strain demonstrated partial susceptibility to disease, as evidenced by histopathology and survival curves. TNFR2 or beta2M gko mice were not susceptible to infection with NCts-8, on the basis of absence of pathology and lack of mortality. Lack of mortality and minimal histopathology scores demonstrated that NC-1, NC-2, and NCts-8 infections were avirulent in IL-10 and iNOS2 gko mice. Adoptive transfer of immune cells from NCts-8 vaccinated normal syngeneic mice into IFN-gamma gko mice significantly (P < 0.05) prolonged mean survival times at all 3 challenge doses of NC-1 but failed to protect against mortality. Interestingly, there was a notable change in the tissue tropism of tachyzoites from the lung and brain in immunocompetent wt, TNFR2 gko, IL-10 gko, beta2M gko, and iNOS2 gko mice to the liver and spleen in IFN-gamma gko mice when challenged with N. caninum. On the basis of these results in gko mice, IFN-gamma is a critical cytokine in the host response against acute neosporosis.     

Les inhibiteurs de la phosphodiestérase de type 5 : une révolution dans le traitement des sympt?mes du bas appareil urinaire?

Context

The incidence of lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH) increases with age, affecting 50% of patients aged over 50 years and 90% of those aged over 80 years. The prevalence and severity of erectile dysfunction (ED) also increase with age. Its prevalence is estimated to be 31.6% in men over 40 years. LUTS as well as ED significantly affect the quality of life of patients and their partners. Several studies have shown that LUTS represent an independent risk factor for ED. The severity of LUTS is correlated with that of ED. The pathophysiological hypothesis linking LUTS to ED are an increase in sympathetic tone, alteration of NO/cGMP system, alteration of rho kinase system, and pelvic atherosclerosis.

Goal

Some treatments of LUTS have adverse effects on the erectile function. The phosphodiesterase type 5 inhibitors (IPDE 5) revolutionized the treatment of ED.

Material and methods

Several recent clinical studies evaluated the effect of daily treatment by IPDE 5 on LUTS secondary to BPH among patients with or without ED.

Results

This review shows that IPDE 5 administration improves LUTS significantly in 12 randomized clinical trials, as well as in both storage and voiding parts of the international prostate symptom score (IPSS) and in quality of life questionnaire. No adverse events were observed, and ED, which has a high prevalence among this population, was also improved.

Conclusion

The treatment of LUTS by IPDE 5 looks very promising, even though they are not yet approved for this indication in France.     

News from the Biological Stain Commission No. 15

In the 15^th issue of News from the Biological Stain Commission (BSC), under the heading of Regulatory affairs, the Biological Stain Commission’s International Affairs Committee presents information from the plenary meetings of the International Standards Organization ISO/TC 212 Clinical laboratory testing and in vitro diagnostic test systems held on August 22–24, 2012 in Berlin, Germany. An additional discussion of the use of food dyes in India also is included.     

Accomplishments of the Trustees and laboratory staff of the Biological Stain Commission, 2002–2013

During the 12 years from 2002 to 2013, the Trustees and laboratory personnel of the Biological Stain Commission (BSC) can claim many accomplishments. These accomplishments are itemized under 11 categories: continuous publication of the official journal, Biotechnic & Histochemistry; production of four special issues of Biotechnic & Histochemistry devoted to specific dyes or stains; standardization of staining and dye purity; mechanisms of staining and prediction of dye behavior; publication of books or book chapters; effects of fixation and processing on staining; cancer research; immunohistochemistry; BSC Laboratory activities; miscellaneous publications; and administrative accomplishments.