Apoptose et spermatogenèse

Onset of spermatogenesis is associated with a wave of apoptosis, which limits its efficacy during the first cycles in most mammals. After the first cycles, the actual efficacy of spermatogenesis always remains below the theoretical yield. Among the germinal cells, spermatogonia are the main targets of physiological apoptosis. This physiological apoptosis partly depends on the relationships between germ cells and Sertoli cells. The impact of the Sertoli cell/germ cell number ratio on the efficacy of spermatogenesis is well accepted, the concept of density-dependent regulation in the seminiferous tubule was proposed in the early eighties. Since the steps of spermatogenesis require a continuous progression of the cell cycle rather than an arrest, germ cells might therefore be more sensitive to apoptosis. This may also lead to severe disturbances between proliferation and cell death. The first experiments designed to elucidate the mechanisms of germ cell apoptosis were based on hormonal deprivation or cryptorchidism. However, the link between hormonal or cellular action and cell survival remained to be established. Analysis of signal transduction pathways involved in germ cell apoptosis and their regulation were the next steps. The involvement of bcl-2 family genes has been confirmed, although the expression of some of its members remains more controversial. Data derived from overexpression of some genes (Bcl-2, Bcl-xl) or resulting from gene inactivation (Bax) at the testicular level have highlighted the role of these genes in the control of germ cell apoptosis and have also provided some evidence for the strict requirement for density-dependent regulation of spermatogenesis. More recently, variations in the pattern of expression of these genes or proteins helped to explain some of the discrepancies in the literature. The place of the Fas/Fas ligand system during the first cycle of spermatogenesis remains a matter of debate, with controversies concerning the precise site of expression of this oncogene and its receptor. Conversely, its role in the testis after chemotoxic or radiotoxic treatments is well established. However, the normal fertility of animals with a spontaneous inactivation of Fas or Fas L genes does not support a physiological role of these factors during spermatogenesis. While factors involved in TNF/TNF R1 (Tumor Necrosis Factor) are under study, some data have been reported concerning the role of TRAIL (TNFalpha Related Apoptosis Inducing Ligand) and its active or decoy receptors in the testis. Among the oncogenes which may modulate the apoptotic process, Kit/Stem Cell Factor is particularly interesting, as Kit is expressed in some germ cells and Leydig cells, whereas SCF is expressed by Sertoli cells. Its impact during gonadal development and in the survival and proliferation of differentiated spermatogonia has been clearly established. Using a transgenic mice model, in which the Kit gene was inactivated by the insertion of a nls-lacZ sequence in its first exon, we showed that one single copy of the gene was unable to sustain physiological spermatogenesis and fertility in male mice. Our results also suggest that the Kit gene might be expressed at different steps of spermatogenesis, with different signal transduction pathways and biological actions. Finally, analysis of the signal transduction pathways involved in testicular apoptosis and their mechanisms of control is one of the key steps to a better understanding of both impairment of spermatogenesis and the pathogenesis of certain germ cell tumours.     

Oestrogènes et reproduction masculine

The role of estrogen on male reproductive function has become clearer in the last decade. During these years the study of the effect of testosterone, estrogen or an aromatase inhibitor in hypogonadal men provided a first evidence of the effects of estrogens in the regulation of gonadotropin secretion. At the same time, the development of a line of transgenic male mice lacking estrogen receptor α, estrogen receptor β or aromatase gene provided further evidence about the role of estrogens not only in the regulation of gonadotropin secretion, but also on the effects of estrogens on testicular function and development. A confirmation of these actions of estrogens came from the observation of naturally occurring mutations of the estrogen receptor and of the aromatase gene in human males. Based on these data it has been demonstrated that estrogens are major regulators of gonadotropin secretion acting both at pituitary and hypotalamic level. The presence in the human reproductive structures of estrogen receptor α, estrogen receptor β and the aromatase enzyme indicates the existence of receptor α, estrogen receptor β or aromatase estrogen actions at this level. Anyway, the precise role of estrogens in testicular development and function and on the regulation of human spermatogenesis has not yet been precisely clarified.     

Androgènes et sexualité masculine

Testosteron is known to be critical for the right maintenance of masculin sexuality. It acts on all components of sexuality: libido, erection and ejaculation. As far as erection is concerned, one has to emphasize on the fact that only spontaneous nocturnal erections are androgen-dependent unlike erectile responses to visual erotic stimuliThe T can act, at the level of target organes, either as unchanged or as more often observed after reduction to DHT or aromatisation to E2. It is essencially as DHT that the male hormone seems to act on the sexuality at both the central and peripherical levels. The oestrogens even if now shown to have no peripherical action, are still subject to controversy as far as their central action is concerned. Therefore an action at the cerebral level of the oestrogens produced locally can not be definitively eliminated.The concentrations of T required for the re-establishment of the sexual function in case of hypogonadism are closer to the lower limits of normal values. The upper treshold of the action of T on the sexuality, if any, would be at supra-physiological levels.Androgenotherapy of sexual dysfonctionnalities is wittnissing a constant evolution. New and more performing products, as well as novel and less astreignant ways of administration, are already disponible or under evaluation. Moreover, the improvement of plasmic androgen exploration (dosage of free and non-sex hormone-binding globulin bound testosterone) associated to a better understanding of side effects of the androgenic therapeutics may allow in the near futur to reach a consensus on the androgenotherapy indications. As a matter of fact among the population of patients considered eugonadic (based on normal levels of T) and showing a sexual dysfonctionality, two subgroups might be interested: That of elderly patients displaying either an increase of the hormone-binding globulin (SHBG) or a decrease of the non-sex hormone-binding globulin bound testosterone levels and that of young patients suffering from idiopathic impotence. It should be, however, pointed at that the recent character of the different physiopathologic and therapeutic acquisitions requires a validation through larger series and long term studies.     

Stress et Spermatogénèse

Stress, which originates in the brain, can influence spermatogenesis hormonally or via the nervous system. The hormonal route commences with the central secretion of Corticotrophin-Releasing Factor, leading to a fall in LHRH production, a decrease in Leydig cell LH receptors and a decrease in 17 a hydroxylase activity. Thus, in the case of major, prolonged stress, testosterone secretion falls, which in turn affects spermatogenesis. However, given that the testosterone threshold required for normal seminiferous epithelium function is significantly less than the mean circulating level of this hormone, the importance of low intensity stress remains unknown. The nervous route involves catecholaminergic fibres which, in the testis, innervate the Highmore corpus, the vessels, the area adjacent to the Leydig cells, and the basement membrane of seminiferous tubules. The experimental destruction of these fibres leads a regression of the seminiferous epithelium. Moreover, the experimental ablation of the rat anterior neocortex leads to changes in spermatogenesis. Therefore, given that the endocrine system does not seem to be involved in these changes, these results indicate that the highest level of the nervous system may participate in the controlling the germinal epithelium which, all things considered, would tend to support psychosomatic influences. However, given that the number of spermatozoa varies significantly between ejaculate and independantly of the level of testosterone secretion necessary for normal spermatogenesis, it may be hypothesized that it is only when sperm production is low that temporary stress, in aggravating the situation, becomes deleterious to spermatogenesis. Since, under normal conditions, such periods are short, the role of the influence of stress on spermatogenesis can only be relative. Nevertheless, if variations occur during permanently low sperm production, the likelihood of negative effects is increased. Consequently, the impact of stress or psychological factors on spermatogenesis might well depend upon particular circumstances.     

Varicocèle et infertilité masculine

Introduction

Male responsibility in couple infertility has been established in several studies. The purpose of this research was to report varicocele clinical and spermatic aspects and assess the outcomes of open retroperitoneal varicocelectomy.

Patients and methods

Our study is a retrospective assessment of the outcomes of open retroperitoneal varicocelectomy at the urology department of Aristide Le Dantec teaching hospital (Senegal). Our focus is on patients with varicocelectomy facing couple infertility (inability for sexually active couples who are not using contraceptive methods to obtain a pregnancy over a year), patients among which no other infertility cause was revealed in their partner or partners in polygamist households. To assess the results, we compared the averages of preoperative and postoperative spermatic parameters by using the Z test (comparison test of two averages on two mated series). A difference was regarded as significant if P ?? 0.05.

Results

Five hundred and fourteen cases were examined over 6 years (January 2005?CDecember 2010). The average age of the patients was 36.5 ± 7.3 years. The infertility was primary in 62.4%. The analysis of the preoperative spermograms revealed that severe oligozoospermia (33.7%) was the most common abnormalities in the sperm cells concentrations. The abnormalities in the sperm cells concentrations were variously connected with an asthenozoospermia and to a theratozoospermia. The patients were monitored with an average hindsight of 22 months (6?C48 months). The improvement of the parameters was more significant on the concentration and the mobility of sperm cells. The natural pregnancy rate obtained in our study was 20.8%. The registered pregnancies were more important in the group IV (48%). No case of natural pregnancy was noted in the group I but an induction of the spermatogenesis was noted in 20.5% of the cases. About two thirds of natural pregnancies (64%) were noted during the first 12 post-operative months.

Conclusion

The surgical treatment of varicocele allows improving the spermatic parameters. Not only do these improvements help obtain natural pregnancies but also simplify the techniques of ART planned with the preoperative spermatic parameters.     

Estrogènes et spermatozoïdes

Aromatase is the terminal enzyme responsible for estrogen biosynthesis; it is present in the endoplasmic reticulum membrane of steroidogenic cells in vertebrates. This enzyme functions with the ubiquitous reductase as the electron donor. The aromatase gene is unique and its expression is regulated in a tissue and more precisely in a cell-specific fashion via the alternative use of several promoters located in the first exons. This enzymatic complex is generally involved in development, reproduction, sexual differentiation and behaviour, but also in bone and lipid metabolism, brain functions and diseases such as breast and testicular tumors. The aromatase gene expression and its transduction in a fully active protein in testicular somatic cells and germ cells together with the widespread distribution of estrogen receptors (ERα & β) in the testis and the genital tract of the male, are clearly in favor of a physiological role for estrogens in the spermatogenesis processings especialy in sperm maturation. Therefore, we begin to understand the physiopathological roles of the estrogens in males indeed, the aromatase deficiency is associated, with severe bone maturation problems and sterility in man. Conversely, it is also obvious that estrogens in excess are responsible of the impaired spermatogenesis. These female hormones (or the ratio androgens/estrogens) do play a physiological role in the development and maintenance of male gonadal functions and obviously, several steps are concerned especially the sperm production and maturation.     

Lamine C2 et spermatogenèse

Lamin A/C are intermediate filaments present in nucleus. Their roles are numerous and laminopathies are issued from LMNA gene mutations. In male germ cells, this protein family is only represented by lamin C2. The results obtained in male mice show the importance of these filaments in male meiosis and suggest the existence of a new male infertility domain involving this intermediate filament and its associated proteins.     

Températures et varicocèles

Varicocele is considered to be responsible for male infertility by several authors, while varicocele may also exist in fertile men. Hyperthermia or “raised” testicular temperature is one of the pathophysiological mechanisms proposed to explain impaired spermatogenesis when a varicocele is present in infertile men. The reported clinical data in humans and experimental results of surgically-induced varicocele in animals indicate the following findings. In most studies, mean testicular and scrotal temperatures are bilaterally increased in populations of men with unilateral left varicocele compared to control populations. Similar results are observed following surgical induction of experimental left varicocele in animals. In the case of bilateral varicocele, the increase in mean temperature is similar to that observed in unilateral varicocele. Data concerning the effects of varicocelectomy on testicular or scrotal temperatures are still inconclusive in humans because of the discordant results in the small number of studies dealing with this topic. However, experimental data indicate that varicocelectomy results in recovery of normal mean temperature in animals submitted to surgically-induced varicocele, but experimental animal models of varicocele have failed to provide any explanation for the increase in temperature. In conclusion, although there is a relationship between varicocele and testicular temperature, testicular temperature is not increased in every case of varicocele.     

Illustrations pratiques — Pièges et artefacts/Trucs et astuces

Artifacts result from discrepancy between the estimated density values coming from the reconstructed CT image and the real value. They may come from many reasons (patient, device, algorithm, RX physical) and lead to deterioration of image quality and bad attenuation correction for SPECT or PET.     

Spermatogénèse et Paraplégie

In this article, the paraplegics’ possibilities for procreation will be examined. A first chapter will deal with the testicle functioning along with the study of hormonal measuring and testicle histology (study involving 100 patients). As a result, it appears that, after a testicle biopsy, there is a testicle lesion of neurological origin that is sometimes irreversible. On the contrary, the endocrinal testicle lesions have proved reversible under stimulation or spontaneously. A second chapter will deal with the different techniques to obtain an ejaculation and the semen analysis. The techniques that were used being: massage by vibrator, electroejaculation, ejaculation through pharmacological stimulation. The study focuses on 124 ejaculatory tests among which 64 forward ejaculations (52%) and 4 bachward ejaculations (3%) were obtained. The resulting semen analysis revealed a spermatozoon count greater than 20 millions per millilitre (that is 51,5%) and smaller than 5 millions in 11 cases (16%).     

Cancer du testicule: BEP et spermatogenèse

The sperm characteristics of 44 men treated with two or more courses of BEP chemotherapy for non seminomatous germ cell testicular tumours were investigated before and 25.2 ± 19.4 months after chemotherapy. Before treatment, 54.5% of patients were oligozoospermic. The mean sperm characteristics did not differ before and after chemotherapy. However, following chemotherapy, the recovery of initial sperm count was more frequent after one year than before. During the first year, recovery was more frequent in patients treated with two than in those treated with more than two BEP cycles. In patients with good pre-treatment sperm count, sperm production was reduced by half after chemotherapy. In a subgroup of men who provided two sperm samples after chemotherapy, sperm production was better in the second sample than in the first. Our data suggest that sperm recovery is related to testicular function prior to therapy, to the time elapsed after chemotherapy and in the first year to the number of chemotherapy cycles. In conclusion, our study is reassuring concerning the long-term male reproductive toxicity of BEP. However, further studies are required to analyse the possible effects on sperm genetic material during the recovery period.     

La reine d'Apis mellifica les ouvrières pondeuses et les constructions cirières

Résumé Une cinquantaine d'abeilles, âgées de six jours, peut construire des alvéoles de cire en présence d'une reine vierge ou d'une reine féconde, ce nombre minimum s'élève à 200 avec une reine morte. En revanche, il faut atteindre une quantité importante d'insectes (10000 environ) pour obtenir des étirages de rayon sans reine. Cependant, la présence d'ouvrières pondeuses permet la construction des édifices de cire avec 5000 abeilles. On fait appel à une substance sécrétée par les reines ou bien les ouvrières pondeuses pour expliquer certains de ces phénomènes. Est-elle semblable à celle signalée parPain? Le parallélisme de nos résultats me porte à le croire.

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Summary 50 Bees, 6 years old, build combs in presence of mated or virgin queens; 200 insects can also construct in presence of a dead one. In return, 10,000queenless bees are necessary to assume the same task. But 5,000 laying workers can build combs. A queen substance is called upon to explain some of these phenomena.Is this andPain's ectohormone the same? The parallelism of our conclusions urge me to think so.

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Zusammenfassung In Anwesenheit einer unbegatteten oder begatteten Königin, zeigen 50 sechstägige Bienen eine deutliche Bautätigkeit. In Anwesenheit einer toten Königin müssen es schon 200 Bienen sein. Ohne Königin fängt erst mit 10000 Bienen die Bautätigkeit an. Mit eierlegenden Arbeiterinnen genügen doch 5000 Bienen. Die Erklärung dieser Tatsache wird in das Vorhandensein einer Substanz gesucht, welche durch die Königin oder durch eierlegenden Arbeiterinnen abgesondert wird. Man vermuttet daß diese Substanz dieselbe ist als diejenige die durchPain gefunden wurde.

     

Synthèses et réductions de sucres fonctionnels mono et diinsaturés

Attempts to prepare 1,2:5,6 and 2,3:5,6 di-unsaturated sugars starting from 3,4,6-tri-O-acetyl-1,5-anhydro-1,2-dideo xy-d-arabino-hex-1-enitol or from ethyl 4,6-di-O-acetyl-1,5-anhydro-2,3-dideoxy-α-d-erythro-hex-2-enopyranoside led to 1,5-anhydro-1,2,6-trideoxy-l-threo-hex-5-enitol and its 3,4-diacetate. Hydrogenation and hydrogenolysis of the unsaturated chloro and fluoro derivatives afforded 1,5-anhydro-1,2,6-trideoxy-d-arabino-hexitol and ethyl 4-O-acetyl-2,3,6-trideoxy-α-d-erythro-hexopyranoside.