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.     

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.     

Comprendre la dépression : apport de la psychologie évolutionniste

Darwinian medicine considers that many symptoms are the organism’s defence mechanisms and adaptations that have been inherited and shaped by natural selection. But in many cases, signs and symptoms of disease are of no benefit to human survival and are in fact deregulations of normal mechanisms. Evolutionary explanations help us understand how some human affective and emotional processes could have an adaptive value and enable us to cope with a wide spectrum of situations. But the wide range of intensity levels and different forms, ranging from low moods to major depression with psychotic features, suggest that these symptoms cannot always be explained by adaptation: where is the cut-off point? In this paper, we describe the evolutionary concepts related to adaptation as applied to the emotions, particularly focusing on low mood and depression, and discuss their possible functional and adaptive role.     

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.     

Place de l’embolisation percutanée de la varicocèle dans le traitement de l’infertilité

Objectives

To describe percutaneous embolization of varicocele and to evaluate the effect on fertility disorders.

Materials and methods

One hundred nineteen patients, aged 11 to 48 years, underwent percutaneous embolization for varicocele indicated by a fertility disorder in 23% of cases. Correction of the varicocele and resolution of associated pain, improvement of testicular trophicity and the effect on fertility were studied and a review of the literature was performed.

Results

Percutaneous embolization was performed using neuroleptanalgesia on an outpatient basis. The technique combined venous sclerotherapy and placement of coils in the gonadal vein. The technique was successful in 95% of cases and one complication was observed. At 3 months, the varicocele and related pain had resolved in 98% of treated patients. According to previous reports in the literature, the relations between varicocele and fertility disorders are still unclear, but improvement of fertility (semen quality and conception rates) after varicocele repair has been established.

Conclusion

Although the consequences of varicocele on fertility have not been fully elucidated, treatment of varicocele appears to be beneficial. Percutaneous embolization of varicocele is a safe and effective alternative to surgery. This technique, based on a urological and radiological consensus, is the first-line treatment for varicocele in our institution.     

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.     

La germination de la zygospore et l'ontogénèse des filaments chez Spirogyra stictica Wille

Sans résumé     

Diminution de la capacité de surfusion au cours de l'embryogenèse et du développement larvaire chez un coléoptère

Potential cold resistance of non-diapause eggs and first instar larvae of Osmoderma eremita (Coleoptera, Cetoniidae, Trichiinae) during embryogenesis and post-embryonic growth was assessed by measuring individual supercooling points (SCP): sterile eggs had a mean SCP of −24.3 ± 2.0 °C; fertilized newly laid eggs a mean SCP of −23.4 ± 3.2 °C and eggs about to hatch a mean SCP of −9.2 ± 2.9 °C. Water absorption by fertilized eggs is a necessary requirement for the development of the embryo and results in an increase in weight and water content: fertilized newly laid eggs had a mean fresh weight of 10.687 ± 1.072 mg and a mean water content (expressed as a percentage of the dry weight) of 79.5 ± 10.83%; eggs about to hatch had a mean fresh weight of 19.127 ± 3.183 mg and a mean water content of 250.10 ± 74.15%. The ex-ovo larvae, hatched 30 days after oviposition, had a mean SCP of −10.1 ± 3.6 °C (no significant difference with eggs about to hatch) and had gained in weight (24.845 ± 3.911 mg) and in water content (499.72 ± 55.49%). Feeding 1st instar larvae had a decreased supercooling ability (mean SCP = −5.7 ± 0.4 °C) whereas their mean fresh weight (99.858 ± 53.091 mg) and mean water content (665.83 ± 82.74%) increased. The eggs and larvae of O. eremita are freezing intolerant. Before overwintering, all larvae switch to being freezing tolerant and can survive ice formation in their tissues and body fluids, whereas their mean SCP stays at around −5 °C. However, recent experiments in the winter of 1996 have shown that frozen larva mortality does occur at temperatures lower than about −12 °C.     

Synthèse d'ARN dans le chondriome au cours de la spermiogenèse chez la Drosophile

Résumé L'incorporation d'uridine-³H dans l'ARN nucléaire et dans l'ARN mitochondrial est détectée à l'aide de l'autoradiographie à haute résolution au cours de la spermiogenèse chez la Drosophile.Le marquage apparaît simultanément sur le noyau et sur le chondriome jusqu'au début de la condensation de la chromatine. Le nebenkern, qui caractérise un des premiers stades de la spermiogenèse, est le territoire cellulaire le plus radioactif. La synthèse de l'ARN nucléaire cesse au cours de la condensation de la chromatine. Pendant ce temps, le marquage des dérivés mitochondriaux se poursuit; il persiste jusqu'à leur complète transformation en paracristal. Ces observations mettent en évidence une synthèse autonome d'ARN par les mitochondries à la fin de la spermiogenèse.

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Autonomous mitochondrial RNA synthesis during spermiogenesis in Drosophila

Summary The incorporation of ³H-uridine into nuclear and mitochondrial RNA has been followed by electron microscope autoradiography during spermiogenesis in Drosophila.Nuclei and mitochondria are simultaneously labeled up to the beginning of the chromatin condensation. The nebenkern, characteristic of the first stages of spermiogenesis, is the most radioactive cellular component. During chromatin condensation, nuclear RNA synthesis ceases, but mitochondrial derivatives continue to be significantly labeled up to their complete paracrystalline transformation. These data show an autonomous RNA synthesis by mitochondria at the end of spermiogenesis.

Ce travail a bénéficié de l'aide du C.N.R.S. (E.R.A. 174), de la D.R.M.E. (contrat 70/414) et du C.E.A. (participation à l'achat de molécules marquées).     

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.     

Contrôle de la détermination et de la différenciation des caractères sexuels somatiques de Néréidiens (Annélides polychètes)

Résumé Les modalités de la détermination et de la différenciation du dimorphisme sexuel de Néréidiens (Annélides Polychètes) ont été recherchées chezNereis pelagica L. etPerinereis cultrifera G. par des expériences de décérébration, de castration (par irradiation X), de greffes et d'injection de produits génitaux.Les caractères sexuels somatiques des cirres parapodiaux (renflement et crénelures) se développent toujours conformément au sexe génétique quel que soit l'état génital de laNereis et la nature de l'intervention. La détermination des caractères sexuels somatiques des cirres parapodiaux apparaît donc comme étant très précoce (3 mois au moins avant la différenciation génitale) et stable.Par contre, les papilles pygidiales, caractère sexuel mâle dans les conditions normales, peuvent se différencier chez les très jeunes femelles dont l'épitoquie est déclenchée prématurément par décérébration et chez les femelles de tout âge dont les transformations hétéronéréidiennes sont réalisées en présence d'un milieu mâle (injection de produits génitaux, greffe sur un mâle). Les papilles pygidiales semblent donc déterminées précocement chez les deux sexes; leur différenciation est cependant inhibée chez les femelles au cours de la maturation génitale.

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Control of determination and the differentiation of the sexual somatic characters of Nereids (Annelida Polychaeta)

Summary The modalities of determination and differentiation of sexual dimorphism of Nereids (Annelida Polychaeta) were investigated inNereis pelagica L. andPerinereis cultrifera G. with experiments involving decerebration, castration (by X irradiation), grafts or injection of genital products.The sexual somatic characters of the parapodial cirri (swelling and crenellations) always develop according to the genetic sex, whatever the genital state of the Nereis and the nature of the intervention. Therefore the determination of the sexual somatic characters of the parapodial cirri appear to be determined in a very precocious and stable way (at least 3 months before the genital differentiation).The pygidial papillae, a male sexual character in normal conditions, can be formed by very young females in which heteronereidation is realized prematurely by decerebration, and by females of any age in which heteronereid transformations are realized in a male environment (e.g. by injection of genital products, or grafting onto a male). Therefore the pygidial papillae may be determined precociously in either sex; however their differentiation is normally inhibited in females in the course of genital maturation.

     

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.     

La photopoïèse d'un carotinoïde rouge préchlorophyllien dans l'évolution normale et la fhysiopathologie des chloroplastes d Aloe

Conclusion Les deux faits que j'ai surtout illustrés: 1. apparition d'un carotinoïde rouge avant la chlorophylle, 2. nécessité de la lumière pour obtenir ce carotinoïde rouge, n'ont pas d'importance chacun en soi-même, isolément. Mais ils se valorisent l'un l'autre et ils acquièrent ensemble une signification physiologique spéciale. Je ne dis pas que ce soit un fait général, pas même pour l'Aloe: assurément ce comportement est sous la dépendance de facteurs internes et externes spéciaux. Mais le fait que ce phénomène existe, et qu'il peut même être provoqué par des moyens faciles et contrôlables, est de nature à ouvrir des perspectives nouvelles aux problèmes de la chlorophyllogénèse, et des rapports biologiques entre chlorophylle et carotinoïdes.