Estrogens: a new player in spermatogenesis.

The mammalian testis serves two main functions: production of spermatozoa and synthesis of steroids; among them, estrogens are the end products obtained from the irreversible transformation of androgens by aromatase. The aromatase is encoded by a single gene (cyp19) in humans which contains 18 exons, 9 of them being translated. In rat the aromatase activity is mainly located in Sertoli cells of immature animals and then in Leydig cells of adults. Moreover rat germ cells represent an additional source of estrogens: the amount of P450arom transcript is 3-fold higher in pachytene spermatocytes (PS) compared to gonocytes or round spermatids (RS); conversely, aromatase activity is more intense in haploid cells. Male germ cells of mice, bank vole, bear and monkey express also aromatase. In man besides Leydig cells, we have shown the presence of a biologically active aromatase and of estrogen receptors in ejaculated spermatozoa and in immature germ cells. Concerning aromatase, a 30% decrease of the amount of mRNA is observed in immotile compared to motile sperm fraction from the same sample; moreover the aromatase activity is also diminished of 34%. In asthenoteratozoospermic and teratozoospermic patients the aromatase gene expression is decreased by 67 and 52%, respectively when compared to normospermic controls. Statistical analyses between the sperm morphology and the aromatase/GAPDH ratio have revealed a high degree of correlation (r=-0.64) between the ratio and the percentage of abnormal spermatozoa (especially microcephaly and acrosmome malformations). Alterations of sperm number and motility have been described in men genetically deficient in aromatase, which together with our data, suggest a likely role for aromatase/estrogens in the acquisition of sperm motility. Therefore besides gonadotrophins and testosterone, estrogens produced locally should be considered as a physiologically relevant hormone involved in the regulation of spermatogenesis and spermiogenesis

Un dispositif pour favoriser l’engagement des étudiants dans la rédaction de leur rapport de stage

Cet article rapporte la mise en place et l’analyse d’un dispositif qui a pour objectif de soutenir l’engagement des étudiants de master Métiers de l’édition dans l’écriture d’un rapport de stage. L’engagement sera étudié à travers le prisme de l’utilité, du sentiment d’efficacité personnelle et des attentes des étudiants (en termes de réussite). Le dispositif repose sur l’ajout i) d’un atelier sur l’identification et la formulation des compétences et ii) d’un rendu fractionné du rapport au dispositif existant (grille d’évaluation critériée et guide de rédaction). Les résultats suggèrent que l’atelier aide les étudiants à mieux appréhender les objectifs du rapport de stage et soutient leur engagement au travers d’une augmentation de la valeur attribuée à la tâche. Le feedback régulier via l’atelier et le rendu fractionné semblent renforcer le sentiment d’efficacité personnelle en améliorant la compréhension des objectifs du rapport de stage et de l’écriture réflexive. Le dispositif se veut également une ressource pour la suite de la carrière puisque les étudiants s’approprient des outils qui devraient favoriser leur insertion professionnelle

Il meticciato nell'Italia contemporanea. Storia, memorie e cultura di massa.

L'idea diffusa degli "italiani brava gente" e della diversit\ue0 della nostra storia rispetto alla storia USA, segnata da razzismo istituzionale, si fonda sul silenziamento del passato coloniale e razzista italiano. Il ripudio della categoria di razza da parte dell'Italia repubblicana e la smentita scientifica dell'esistenza biologica della categoria non hanno cancellato la presenza della razza, formazione storico-culturale che paradossalmente esiste e non esiste. Priva di referenti oggettivi nella realt\ue0, la razza produce in essa effetti significativi, opera sia come categoria sociale e strumento di esclusione, sia come costruzione simbolica e istanza identitaria. A fronte del silenziamento del meticciato storico nell'uso pubblico della storia e nella memoria nazionali del secondo dopoguerra, il saggio sottolinea la presenza diffusa del meticciato nei prodotti della cultura di massa italiani contemporanei e ne indaga i significati con gli strumenti degli studi critici sulla razza e in prospettiva comparata tra Italia e Stati Uniti

Estrogènes et spermatogenèse chez le rat (Thèse soutenue sur un ensemble de travaux)

La spermatogenèse, le processus permettant la formation des gamètes mâles, est sous le contrôle de nombreux facteurs et les estrogènes semblent être impliqués dans la régulation de ce mécanisme ainsi que dans sa mise en place. Les données de localisation de l aromatase et des ESRs dans le testicule de rat étant discordantes, nous avons réalisé une cartographie précise de leurs messagers et protéines dans le testicule de rat et nous avons montré que leur expression y est régulée finement. Ensuite, nous nous sommes intéressés au(x) rôle(s) potentiel(s) des estrogènes dans la spermatogenèse. Nous avons donc développé un modèle de culture de tubes séminifères de rats permettant de conserver les interactions physiques au sein de l épithélium séminifère. Le 17b-estradiol (E2) (10-9M) induit une augmentation de l expression des gènes des cyclines A1 et B1, spécifiquement dans les stades IX-I et cet effet impliquerait les ESRs et GPER, exprimés dans le testicule de rat adulte. A 30 jours, (mise en place de la première spermiogenèse), l E2 (10-9 M) induit une diminution de l expression des gènes des cyclines A1 et B1 qui ferait intervenir GPER. Par immunolocalisation, nous avons montré que le testicule de 30 jours exprime faiblement ESR1 mais très fortement GPER et ESR2. L analyse des séquences promotrices des gènes des cyclines, a mis en évidence l absence d éléments de réponse aux estrogènes et la présence de sites potentiels de régulation faisant intervenir d autres facteurs de transcription. Ainsi l E2 a un rôle et mettrait en jeu des acteurs différents en fonction de l âge dans le contrôle de la balance différenciation/apoptose dans la spermatogenèse de rat.Spermatogenesis, the process allowing male gametes formation, is under the control of numerous factors and estrogens seem to be implicated in the regulation of this mechanism and in its establishment. Data concerning aromatase and ESRs localization within the rat testis are in conflict, so we have realized the precise cartography of their transcripts and proteins in the rat testis and we have shown that their expression is very finely regulated. Then, we studied the potential role of estrogens in spermatogenesis. We have developed a culture model of rat seminiferous tubules allowing the preservation of physical interactions within the seminiferous epithelium. 17b-estradiol (E2) (10-9M) induces an increase of cyclins B1genes expression specifically in stages IX-I and this effect may involve ESRs and GPER, expressed in the adult rat testis. At 30 days (establishment of the first spermiogenesis), E2 (10-9M) triggers a decrease of cyclins A1 and B1 genes expression which may implicate GPER. Using immunolcalization, we have shown that 30 day-old rat testes express weak amounts of ESR1 and strong levels of GPER and ESR2. The analysis of cyclins A1 and B1 promoting sequences revealed the absence of estrogen response element and the presence of potential regulation sites involving other transcription factors. Thus, E2 plays a differential role and could involves different actors according to the age in the control of proliferation/apoptosis/balance in rat spermatogenesis.CAEN-BU Sciences et STAPS (141182103) / SudocSudocFranceF

Le Diplôme Universitaire « Pédagogie dans l'Enseignement Supérieur » : un exemple de collapération

International audienceDans ce travail, nous proposons un retour d’expérience sur le dispositif pédagogique instauré dans le cadre du Diplôme Universitaire « Pédagogie de l’Enseignement Supérieur » porté par l’Institut de Développement et d’Innovation Pédagogique de l’Université de Strasbourg. Il s’agit d’une formation pour les enseignants dans laquelle ils sont amenés à mettre en place un projet pédagogique spécifique et d’évaluer les changements qu’il induit. Pour accompagner l'enseignant dans cette démarche, le DU était organisé autour de plusieurs moments clés : entretiens individuels, regroupements en promotion complète et ateliers de formation. Nous nous sommes donc demandés si ces moments favorisent plutôt l’apprentissage par la collaboration ou par la coopération. Pour répondre à cette question, nous avons soumis un questionnaire aux 13 participants au DU, 7 réponses ont été obtenues. A la lumière de ces dernières, il semble plus pertinent de représenter le moment d'apprentissage notamment comme un continuum entre coopération et collaboration. Les moments se répartissent en effet selon ces deux modalités, ce qui suggère in fine de considérer le dispositif pédagogique comme une méthode d’apprentissage “collapérative”

17β-Estradiol regulates cyclin A1 and cyclin B1 gene expression in adult rat seminiferous tubules

International audienceSpermatogenesis, which is the fundamental mechanism allowing male gamete production, is controlled by several factors, and among them, estrogens are likely concerned. In order to enlighten the potential role of estrogen in rat spermatogenesis, seminiferous tubules (ST) from two groups of seminiferous epithelium stages (II-VIII and IX-I) were treated with either 17β-estradiol (E(2)) agonists or antagonists for estrogen receptors (ESRs). In this study, we show that cyclin A1 and cyclin B1 gene expression is controlled by E(2) at a concentration of 10(-9) M only in stages IX-I. This effect is mimicked by a treatment with the G-protein coupled estrogen receptor (GPER) agonist G1 and is abolished by treatment with the ESR antagonist ICI 182 780. Moreover, using letrozole, a drug that blocks estrogen synthesis, we demonstrate that these genes are under the control of E(2) within rat ST. Thus, germ cell differentiation may be regulated by E(2) which acts through ESRs and GPER, expressed in adult rat ST

Méthodes haut-débit en toxicologie et en évaluation des risques sanitaires

International audienceToxicology is changing its experimental approaches from animal testing to less expensive, more ethical and relevant methods. From the beginning of this century, various regulations and research programs on both sides of the Atlantic have pushed and contributed to this change. Modern toxicology relies on two main components: in vitro testing and in silico analyses. Toxicology has also entered a world of “big data” production, switching from a low-throughput to a high-throughput mode of screening. Complementary to the assessment of toxicological impact, a large effort has also been made to evaluate human exposure to chemicals: new human and field surveys, analytical measurements, computational capacities, and the use of mathematical modeling have open new possibilities for exposure assessment. Accounting for several sources and routes of exposures, estimating combined exposure to mixtures, integrating exposure variability, and simulating long-term exposure are new challenges on their way to be solved. In addition, biomonitoring data, internal exposure biomarkers, and toxicokinetics are all adding to the list of tools and techniques helping to link the pieces of the yet incomplete puzzle of high-throughput risk assessment. Yet, high-throughput applications in toxicology have been criticized, for their inadequate representation of the biological interactions at the organism level, for the experimental noise they suffer from, for the complexity of the in vivo to in vitro extrapolation and for their yet undefined validation protocols. We propose here a brief panorama of those developments.Les approches expérimentales en toxicologie sont en train de passer de l’expérimentation animale à des méthodes moins coûteuses, plus éthiques et pertinentes. Dès le début de ce siècle, différents programmes de recherche et réglementations des deux côtés de l’Atlantique ont contribué à ce changement. La toxicologie moderne repose sur deux éléments principaux: les tests in vitro et les analyses in silico. La toxicologie s’est également lancée dans la production de données à grande échelle, passant d’un faible débit à un mode de criblage haut-débit. D’une manière complémentaire à l’évaluation de l’impact toxicologique, un effort important est également fait pour évaluer l’exposition humaine aux substances chimiques. De nouvelles enquêtes de consommation, de nouveaux dosages analytiques, des capacités de calcul plus importantes, ainsi que l’utilisation de la modélisation mathématique ont ouvert de nouvelles possibilités pour l’évaluation de l’exposition. Malgré le grand nombre de sources et de voies d’exposition, l’estimation de l’exposition aux mélanges, l’intégration de sa variabilité, et la simulation des expositions à long terme sont de nouveaux défis en voie de résolution. De plus, les données de biosurveillance, les biomarqueurs d’exposition interne, et la toxicocinétique sont des outils qui aident à compléter le puzzle d’évaluation à haut débit des risques. Pourtant, les applications à haut débit en toxicologie ont été critiquées pour leur représentation inadéquate des interactions biologiques au niveau de l’organisme, les incertitudes dont elles sont entachées, la complexité de l’extrapolation in vivo-in vitro et à cause de leurs protocoles de validation encore mal définis. Nous présentons ici un bref aperçu de ces développements

New tools for evidence-based risk assessment of chemical mixtures

Risk assessment of chemical mixture has brought a number of scientific challenges, e.g. with respect to relevant data collection and robust quantitative methods to assess risks in humans. In this talk, the challenges will be presented in both regulatory and scientific viewpoints. Then, new tools for evidence-based risk assessment of chemical mixtures will be discussed in the context of the application of the systematic review methodology and meta-analysis to integrate metabolic interactions and toxicodynamic interactions for substances of priority in the food safety area. Examples of application and perspectives for embedding such techniques in routine risk assessment bodies will be presented

Estrogens: a new player in spermatogenesis.

The mammalian testis serves two main functions: production of spermatozoa and synthesis of steroids; among them, estrogens are the end products obtained from the irreversible transformation of androgens by aromatase. The aromatase is encoded by a single gene (cyp19) in humans which contains 18 exons, 9 of them being translated. In rat the aromatase activity is mainly located in Sertoli cells of immature animals and then in Leydig cells of adults. Moreover rat germ cells represent an additional source of estrogens: the amount of P450arom transcript is 3-fold higher in pachytene spermatocytes (PS) compared to gonocytes or round spermatids (RS); conversely, aromatase activity is more intense in haploid cells. Male germ cells of mice, bank vole, bear and monkey express also aromatase. In man besides Leydig cells, we have shown the presence of a biologically active aromatase and of estrogen receptors in ejaculated spermatozoa and in immature germ cells. Concerning aromatase, a 30% decrease of the amount of mRNA is observed in immotile compared to motile sperm fraction from the same sample; moreover the aromatase activity is also diminished of 34%. In asthenoteratozoospermic and teratozoospermic patients the aromatase gene expression is decreased by 67 and 52%, respectively when compared to normospermic controls. Statistical analyses between the sperm morphology and the aromatase/GAPDH ratio have revealed a high degree of correlation (r=-0.64) between the ratio and the percentage of abnormal spermatozoa (especially microcephaly and acrosmome malformations). Alterations of sperm number and motility have been described in men genetically deficient in aromatase, which together with our data, suggest a likely role for aromatase/estrogens in the acquisition of sperm motility. Therefore besides gonadotrophins and testosterone, estrogens produced locally should be considered as a physiologically relevant hormone involved in the regulation of spermatogenesis and spermiogenesis