Aspects ultrastructuraux de la glande mammaire de lapine pendant la lactogénèse

Résumé L'évolution de l'ultrastructure de la cellule épithéliale mammaire de la Lapine est décrite au cours de:L'apparition des phénomènes sécrétoires qui prennent place normalement pendant le premier tiers de la gestation des Lapines primipares.La lactogénèse expérimentale produite par des injections de prolactine à des Lapines pseudo-gestantes.L'ultrastructure de la cellule mammaire de Lapine en sécrétion active (lactation) se distingue de celle des cellules inactives pour la sécrétion (début de la gestation et pseudogestation) par: le développement considérable de l'ergastoplasme organisé en lamelles parallèles ou concentriques; l'hypertrophie de l'appareil de Golgi; la présence de granules protéiques inclus dans des vacuoles d'origine golgienne au sein d'un cytoplasme hypertrophié, celle des gouttelettes lipidiques étant moins indicatrice d'un état d'activité sécrétoire.L'induction de la sécrétion lactée au cours de la gestation normale ou à la suite de l'injection de prolactine, conduit à des modifications ultrastructurales de la cellule mammaire qui se caractérisent principalement par le développement progressif des systèmes membranaires ergastoplasmiques, qui est déjà net entre 12 et 24 heures et aboutit le 3e jour de l'administration hormonale à des images se rapprochant de celles d'une cellule de glande mammaire en lactation. La formation d'un important réticulum endoplasmique auquel est liée la majorité des ribosomes, ainsi que le développement des citernes et vacuoles golgiennes, paraissent ainsi sous le contrôle de la prolactine. Nous discutons enfin de la signification de l'existence transitoire dans les premiers stades de la lactogénèse d'une organisation vacuolaire de l'ergastoplasme.

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Ultrastructural aspects of the rabbit mammary gland during lactogenesis

Summary The ultrastructural development of the rabbit epithelial mammary gland cell is described during:The appearance of secretory phenomena usually occuring in primiparous rabbits in the last third of pregnancy.Experimental lactogenesis induced by injecting pseudopregnant rabbits with prolactin.The ultrastructure of the active secretory (lactating) rabbit mammary gland cell is distinguished from that of inactive epithelial cells (beginning of pregnancy or pseudo-pregnancy) by: a considerable development of the ergastoplasm organized in parallel or concentric lamellae; hypertrophy of the Golgi apparatus; the presence of protein granules included in vacuoles of Golgian origin in the middle of hypertrophied cytoplasm. The presence of lipid droplets is less indicative of an active secretory state.The induction of milk secretion during normal gestation or after a prolactin injection produces ultrastructural modifications in the mammary gland cell which are characterized by progressive development of the ergastoplasmic membrane system. This transformation becomes evident between 12–24 hours and on the third day of hormonal administration resembles that of the lactating mammary gland. The formation of a large endoplasmic reticulum to which the majority of ribosomes are bound and the development of cisterns and Golgi vacuoles appear under the influence of prolactin. The signification of the temporary existence, during the early stage of lactogenesis, of a vacuolar ergastoplasmic organization, is discussed.

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Les tirages photographiques sont dus à Messieurs Scandolo et Amar que nous remercions vivement.     

Etude de la cholangiogénèse chez le foetus humain

Résumé Les auteurs, étudiant les régions périportales et centrolobulaires des foies d'un embryon et de quatre foetus humains, tendent à préciser quelques aspects de la formation des canaux biliaires intrahépatiques. Ils apportent ainsi une nouvelle contribution à la théorie hépatogène de la cholangiogénèse intrahépatique.

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Summary The present study describes the fine structure of tubules surrounded by parenchymal or biliary epithelial cells at the margin of the centrolobular or portal spaces. The hepatogenic theory of intrahepatic cholangiogenesis is discussed.

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Travail subventionné par le «Fonds National Suisse de la Recherche Scientifique», requête N 3731.

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Avec la collaboration technique de Mlles J. Braeutigam et M.-M. Bertholet et de Mme M. Schreyer.     

Etude de la cholangiogénèse chez le foetus humain

Résumé Les auteurs, étudiant les diverses cellules épithéliales rencontrées dans la région périportale du foie foetal humain, décrivent deux types d'éléments qui possèdent des caractères ultrastructuraux intermédiaires entre ceux de la cellule épithéliale biliaire et ceux de l'hépatocyte.Ils décrivent un type cellulaire à cytoplasme et noyau fortement denses, différents de ceux que l'on observe dans les «dark cells» de Steiner et coll. (1962b).

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Summary The fine structure of the different cells at the margin of the portal spaces was investigated in the foetal human liver. Two types of cells intermediate between biliary epithelial and parenchymal elements were described.In addition, a type of cell in which both the cytoplasm and nucleus are electron-dense was observed. This element is different from the dark cell of Steiner et al. (1962b).

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Travail subventionné par le «Fonds National Suisse de la Recherche Scientifique», requête N 3731.

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Avec la collaboration technique de Mme M. Schreyer et de Mlle M.-M. Bertholet.     

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.     

Hypothèse : le modèle du lieu de rencontre pour la maladie des prions

Prions are responsible for spongiform diseases such as scrapie and bovine spongiform encephalopathy. It is now generally accepted that the disease mechanism involves the conversion from the normal form, PrP^C, to the pathogenic form, PrP^Sc, and that this isoform is infectious. In the case of scrapie, 15 different forms of the disease have been described and some of these different phenotypes can be conferred by infectious prions that are themselves encoded by normal genes. We propose here that a prion with an altered structure has a correspondingly altered preference for lipids; this altered preference creates a proteolipid domain containing different lipids and other factors such as chaperonins and enzymes responsible for post-translational modifications. Normal prions associated with this abnormal domain adopt the conformation dictated by its lipidic composition (and by the other factors present) and so acquire the lipidic preference of the original pathogenic prions. These transformed prions could then create new proteolipid domains. This process may be considered as semi-conservative replication in which prion and lipids are analogous to the Watson and Crick strands and the proteolipid domain to the double helix itself.     

Facteurs impliqués dans le remodelage de la chromatine au cours de la spermiogenèse

Round spermatids are post-meiotic cells with a haploid genome contained in a nucleus, with a structure initially similar to that of the somatic cell nucleus. During spermatogenesis, the spermatid nucleus undergoes drastic remodelling during which it first elongates and then condenses into the very specific and tightly packaged structure of the sperm nucleus. During this remodelling dthe histones are replaced by transition proteins, which, in turn, are replaced by protamines, the specific nuclear proteins of the spermatozoa. Immediately prior to their replacement, the histones are hyperacetylated. The first part of our work was to precisely characterise the changes in histone acetylation during murine spermatogenesis. We have shown that the core histones H2A, H2B, H3 and H4 are hyperacetylated in the elongating spermatids. We have also shown that these changes in acetylation are associated with degradation of the enzymes responsible for histone deacetylation, histone deacetylases or HDACs, while histone acetyl transferases are still present in these cells. The histone acetylation pattern was also investigated during human spermatogenesis, revealing that histone hyperacetylation in the nucleus of elongating spermatids, which appears to be conserved during the course of evolution, also occurs during human spermatogenesis. Moreover, our data obtained from the testes of men with severely altered spermatogenesis, including SCO syndromes (Sertoli Cells Only Syndromes), show that a global hyperacetylation of the Sertoli cell nuclei is associated with an absence of meiotic and post-meiotic cells. This suggests that the global histone acetylation variations observed during spermatogenesis are part of a signalling pathway involving germ cell — Sertoli cell communication. Altogether, these data provide a basis for a better understanding of the mechanisms and identification of the factors involved in post-meiotic remodelling of chromatin.     

Place des troubles de la spermatogenèse dans l’hypofertilité masculine

According to Thonneauet al., (1991), 14% of couples are subfertile. In at least 59% of the cases, a male factor was involved. This indicates that 8% (14% × 59%) of men are hypofertile. Since several causes can induce male infertility and because of the heterogeneous criteria and classifications used in the literature, the percentage of each etiologic factor has not been very precisely established. In a population of 2072 consecutive patients we identified an alteration of spermatogenesis in 52% of the cases. This indicates that about 4% of men might have a spermatogenic problem. The spermatogenic insufficiency was isolated in 43% of the cases (i.e. 23% of the total population) or associated with post-testicular causes of male infertility (infectious/inflammatory; autoimmune; obstructive) in 57% of the cases (i.e. 30% of the total population studied). An etiologic factor is clinically identified for 64% of the patients presenting with a spermatogenic insufficiency. The most relevant risk factors linked to spermatogenic alteration were history of mumps orchitis (OR [IC95%]=14,6 [3,4–62,3]), history of radiotherapy-chemotherapy (OR=14,7 [3,4–63,2]). These situations were found with a low frequency (1,4% and 1,3% of the cases respectively) but provoked a spermatogenic alteration in a large majority of cases (92,9% and 92,3% respectively). On the other hand, varicoceles (OR=3,7 [2,9–4,8]) and troubles in testicular descend (OR=2,9 [2,3–3,7]), were more frequent (20,6% and 20,1% of the cases respectively), but less frequently associated with spermatogenic insufficiency (in 73,7 and 69,6% of the cases).     

La dépression et le traitement antidépresseur: de la neurotoxicité à la neurogenèse

Major depressive disorder is characterized by structural and neurochemical changes in limbic structures, including the hippocampus that regulates mood and cognitive functions. Hippocampal atrophy is observed in patients with depression: structural changes in the hippocampus associated with depression include dendritic atrophy, decreased adult neurogenesis and reduced volume. Impairment of neuroplasticity in the hippocampus, amygdala and cortex is hypothesized to be the mechanism by which cognitive function, episodic verbal memory and emotions are altered in depression. Chronic stress exposure and depression leads to hippocampal atrophy and cell loss as well as to decreased expression of neurotrophic growth factors. All types of antidepressant drugs reverse or block the effects of stress. Chronic antidepressant administration upregulates neurogenesis and neuroplasticity in the adult hippocampus and these cellular responses are required for the effects of antidepressants in animal models of depression.     

L'analyse et la synthèse en systématique végétale

Analysis and synthesis have been widely used in systematics since, at least, the XIXth Century. Even now, the four major authors (Cronquist, Dahlgren, Takhtajan, Thorne) of angiosperm systems use “synthetic” to qualify their classifications. This word — synthetic or synthesis — has many different meanings that can create ambiguity. Among these meanings, is there one that can be justifiably used to define biological classifications? Although much more than the following applications can be found in the botanical literature, this paper will mainly deal with six meanings which are still in use in contemporary systematics. A synthetic classification has been understood as a classification built upward, from the lower to the higher categories. If we define synthesis as the operation that starts with elements and proceeds to a whole, then upward classification could be viewed as a synthesis in which the concept of hierarchy plays a primordial role, a role that is not initially a part of synthesis. Moreover, synthesis cannot replace all classificatory processes, and other criteria of taxa must be used in addition to synthesis Historically, synthesis has replaced analysis; the latter being employed by Linnaeus in his sexual system. Indeed, Linnaeus used a divisive method in producing his classification; and since division was seen as synonymous to analysis and recognized as a method that led to artificial taxa, leading French taxonomists Adanson, Lamarck and A.-L. de Jussieu among others, rejected analysis and viewed their classifications as synthetic, i.e., based on the natural method. Therefore, a system of value took place: natural was better than artificial, synthesis better than analysis. Reinforcing the importance of synthesis was the belief in a concept widely accepted at the end of the XVIIIth Century: that of continuity. Linking groups and forming a continuum was a procedure eminently synthetic. Such a procedure, known as “chaining”, produced series or sequences of taxa. Analysis was used solely to express the idea of dichotomous or analytical keys, a Lamarckian innovation that enabled taxonomists to identify plants. But whether classifications are built from lower to higher categories (a synthesis of taxa) or from higher to lower categories (an analysis of taxa), another simultaneous, concomitant movement is implied: with the latter, a synthesis of characters, with the former, an analysis of characters. Therefore, a synthetic classification is nevertheless an analytical classification.Basing groups on resemblance instead of difference, results in yet another application of synthesis. This application is probably due to the analogy with “composition”. Already, a separation between resemblance and difference among characters is an analysis. More important, still, is that at a certain rank some characters are used to join whereas, at another rank, they separate. Thus, depending on ranks and taxa, characters are applied in a synthetic or analytical procedure. Here also, other criteria are needed to support group delimitation.In connection with the upward (synthetic) movement in classifying taxa, the use of a great number of characters was also considered to be synthesis. This has been a recurring theme in taxonomy over the last two centuries and was sometimes seen as the Gilmourian approach to classification. When would we be justified to talk about synthesis? After how many characters? In fact, it is not the number of characters that matters but how characters are handled. The use of many characters has been closely linked to the idea of natural groups and its joining with synthesis seems to derive from the association of “natural” and “synthetic”.Synthetic classifications equally imply the common idea that they must represent a résumé of information stemming from all biological fields or disciplines. If classifications portray evolution, as many systematists suggest, then it cannot be just a résumé. And one must first decide what classifications are about: a controversial subject among different schools of thought in taxonomy. This explains another meaning attached to synthesis. Biological classifications have been said to be a synthesis or résumé of two types of information: that of similarity and that of phylogeny. Anagenesis is sometimes viewed as incremental to classification and makes up for a third type of information. Even though taxonomists would (for once!) agree that a classification should be based on phenetic, cladogenetic and anagenetic data, such a classification cannot qualify as a synthesis since it is not a composition and does not meet the definition given above (an operation that starts with elements and goes on to a whole). It is impossible to represent these three types of data together in one classification scheme; they express three, sometimes irreducible, points of view. For such a classification, the word “eclectic” is preferable and closer to reality.The use of synthesis as one term of the dialectical movement has made hesitant steps in taxonomy. Indeed, the two opposed theses that evolve into the synthesis are hardly met in classification and the “dialectical” synthesis promulgated by a few taxonomists can be referred back to synthesis as a résumé.Is classification synthetic because it appears to be based on inductive procedures, as it is sometimes implied by different authors who link deduction and analysis (stemming from downward classification)? In logic, synthesis is sometimes (and questionably so) associated with deduction. Moreover, synthesis cannot follow from induction which deals, for example, with the universality of characters. In that sense, there is no composition and so no synthesis. Thus, although induction has been part of classification, it is not a synthetic method.Apart from the ambiguity originating from the multiple meanings of the word “synthesis” in the context of taxonomy, synthetic classifications do not fully express all the complexity and procedures that lead to it. Actually, a classification is as much a synthesis as an analysis. Both methods are complementary, and should not be opposed as is sometimes the case. This opposition was implicit in the debate between Linneans and Jussieans, surrounding the development of the natural method. If one wants to use “synthetic”, then one should be explicit about its meaning. Taxonomists should also be aware of the incompleteness of synthesis in constructing a classification and should be careful not to create a system of value based upon philosophical ground. They should always prefer a complementary mode of thinking when feasible, instead of an “either-or” approach.     

Imagerie de la néoangiogenèse en médecine nucléaire

The formation of new vessels, a process referred to as neoangiogenesis, is one of the key pathophysiological mechanisms in the development and progression of cancer. It contributes to tumour growth and dissemination of neoplastic cells and can determine response or resistance to anticancer therapies. It involves different signaling pathways including the vascular endothelial growth factor (VEGF) pathway and integrins, which are also preferred targets for the development of antiangiogenic therapies. Changes in the microvasculature induced by antiangiogenic treatments occur before morphological changes can be detected with conventional imaging approaches. The development of molecular tools enabling an assessment of these targets before initiating therapy, or early detection of response or recurrence during or following treatment is essential for the close monitoring of antiangiogenic treatments. These outstanding needs call for the development of specific probes enabling the characterization of the molecules and pathways involved. This review summarizes the major signaling pathway involved in promoting tumor neoangiogenes is, the different radiotracers recently developed in preclinical and clinical settings, as well as their potential use in humans in order to improve the management of patients treated with antiangiogenic treatments.     

Apoptose au cours de la spermatogenèse et dans le sperme éjaculé

It has become clear in recent years that programmed cell death occurs spontaneously in the cycle of the seminiferous epithelium. Induced germ cell apoptosis occurs at specific stages of the spermatogenic cycle and the existence of supracellular control of germ cell death during spermatogenesis has been documented. If apoptosis is a key phenomenon in the control of sperm production, the existence and role of apoptosis in ejaculated sperm cells remain controversial. Apoptosis — as determined by DNA fragmentation (TUNEL) and ultrastructural analysis — is abnormally frequent in the sperm cells of the ejaculate of sterile men with classical biochemical and ultrastructural pattern. In this review, we discuss the possible origins of DNA damage in ejaculated human spermatozoa and the consequences of DNA damage if the apoptotic spermatozoa is used for ICSI. Percentages of DNA fragmentation in human ejaculated sperm are correlated with fertilization rates both after FIV and ICSI. Detection of DNA fragmentation in human sperm could provide additional information about the biochemical integrity of sperm and may be used in future studies for fertilization failures not explained by conventional sperm parameters. However, the analysis of other molecular markers of apoptosis (Fas, Annexine V ...) is necessary to assess the role of apoptosis in human ejaculated sperm cells.     

Les ultrastructures nucléaires de la Noctiluque (Dinoflagellé libre) au cours de la sporogenèse

The trophozoït of Noctiluca miliaris has a large nucleus (30 ) with several nucleoli of considerable size that contain DNA fibrillae lying in the interspaces. — Before and during the first sporogenetic divisions, the nucleoli disintegrate, releasing towards the cytoplasma numerous groups of ribonucleic granules passing through the nuclear ampullae. At the end of the sporulation, there are no nucleoli visible in the nuclei and no ampullae. — The nucleoplasm diminishes, as the DNA filaments are built up, to form the meshes of a network which limit the masses of chromatic material that take the shape of chromosomes characterized by regular fibrillar arches, at the 8–16 nuclei stage. In their centre, there is an axial structure which remains intact during the chromosomal segregation; its function during mitosis seems to be important: supplementary layers of arches appear at this level. — The progressive condensation of the chromosomes is correlated to the sporogenetic evolution of the nuclei, not to the different phases of the mitotic cycle. — The karyokinesis is brought about, during early stages, by mere splitting of the chromatic mass and of its envelope, and later one by separation into two lots of chromosomes. The segregation of these chromosomes is effected by partial intervention and growth of the envelope of the nucleus; there is no centromeric structure visible. At the end of divisions, the nucleus is almost entirely formed by its chromosomes. — The nucleolar structure, the karyokinesis, the structure of the nuclear envelope and the chromosomal cycle show the particularly high evolution of Noctiluca, within the Dinoflagellata.     

Anomalies postnatales du développement de la spermatogenèse associées aux troubles de la migration testiculaire

Cryptorchidism, a non-descended testis in its physiological intrascrotal location, is one of the most frequent congenital anomalies of the male genital system. The mechanisms of the normal descent of the testis are still unclear. Several etiological hypotheses have been proposed for cryptorchidism. Cryptorchidism is associated with a greater risk of testis cancer, and is also a cause of impairment in sperm parameters and fertility in the adult age. In this article, we review the cellular and hormonal events occurring from birth to puberty in isolated cases of congenital cryptorchidism that will later, in adulthood, alter both spermatogenesis and fertility.     

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.     

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.     

Etude cytochimique de la spermatogenèse chez Lithobius forficatus L. (Myriapode Chilopode)

Résumé L'étude cytochimique de la spermatogenèse a été envisagée, d'un point de vue qualitatif chez Lithobius forficatus L. (Myriapode Chilopode). Les cellules de la lignée mâle sont de nature essentiellement protéique. On peut distinguer trois grandes périodes: 1. la croissance spermatocytaire, caractérisée par la synthèse d'ARN et de protéines basiques, 2. les phases de division de maturation, 3. la spermiogenèse, marquée par la diminution progressive de la teneur en ARN et en histones.

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Cytochemical study of spermatogenesis in Lithobius forficatus L. (Myriapoda Chilopoda)

Summary A qualitative cytochemical study was carried out of Spermatogenesis in Lithobius forficatus L. (Myriapoda Chilopoda). The gametes are characterized by their protein nature. Spermatogenesis can be divided into three major periods: 1. Spermatocyte growth, a phase of synthesis of RNA and basic proteins, 2. period of maturation divisions, 3. spermiogenesis, characterized by a gradual decrease in the amounts of RNA and histone.

     

Aspects moléculaires de la spermatogenèse: la réparation post-réplication de l’ADN et le système ubiquitine

Ubiquitin is a ubiquitous and highly conserved protein of 76 amino acid residues, that can be covalently attached to cellular acceptor proteins through a multi-step enzymatic pathway. Mono- or poly-ubiquitination of proteins can lead to protein degradation or modification of protein activity. The ubiquitin system is essential to all eukaryotic cells. Many components of the complex ubiquitin system show remarkable evolutionary conservation, from yeast to mammalian species. Interestingly, during gametogenesis, many specialized and important aspects of the ubiquitin system become apparent. TheHR6B gene is a mammalian, autosomal homolog of theSaccharomyces cerevisiae geneRAD6 encoding a ubiquitin-conjugating enzyme.RAD6 in yeast is required for a variety of cellular functions, including sporulation, DNA repair, and mutagenesis. Male infertility inHR6B knockout mice is associated with impairment of spermatogenesis. Components of the ubiquitin system appear to be involved in different steps and processes during gametogenesis, including control of meiosis, and reorganization of chromatin structure.