Réception du modèle divisionnel en France au début des années soixante-dix à la lumière de l'étude des pratiques

Introduction Du milieu des années soixante à la crise de 1974, l'industrie française a connu un important mouvement de concentration s'appuyant sur des fusions qui furent l'occasion d'une transformation des pratiques de gestion que les courants « modernisateurs » appelaient de leurs vœux depuis le début de la décennie. Dans un contexte de préparation des entreprises françaises à l'intensification supposée de la concurrence avec le renforcement du Marché commun et de reconnaissance de la prédo..

Archives et sciences sociales

Séminaire collectif sous la responsabilité d’Éric Brian, Jean Jamin, directeurs d’étudesMorgane Labbé, Pap Ndiaye, maîtres de conférencesVincent Duclert, professeur agrégé Expériences III La première séance de l’année a porté sur le rôle et l’importance des archives dans l’édition. Animée par Vincent Duclert et Jean Jamin, elle a donné successivement la parole à Jacques Revel qui a longtemps co-dirigé la collection « Archives » de Julliard/Gallimard, puis à Hugues Pradier qui dirige actuellem..

Conserved Usage of Alternative 5′ Untranslated Exons of the GATA4 Gene

BACKGROUND:GATA4 is an essential transcription factor required for the development and function of multiple organs. Despite this important role, our knowledge of how the GATA4 gene is regulated remains limited. To better understand this regulation, we characterized the 5' region of the mouse, rat, and human GATA4 genes. METHODOLOGY/PRINCIPAL FINDINGS:Using 5' RACE, we identified novel transcription start sites in all three species. GATA4 is expressed as multiple transcripts with varying 5' ends encoded by alternative untranslated first exons. Two of these non-coding first exons are conserved between species: exon 1a located 3.5 kb upstream of the GATA4 ATG site in exon 2, and a second first exon (exon 1b) located 28 kb further upstream. Expression of both mRNA variants was found in all GATA4-expressing organs but with a preference for the exon 1a-containing transcript. The exception was the testis where exon 1a- and 1b-containing transcripts were similarly expressed. In some tissues such as the intestine, alternative transcript expression appears to be regionally regulated. Polysome analysis suggests that both mRNA variants contribute to GATA4 protein synthesis. CONCLUSIONS/SIGNIFICANCE:Taken together, our results indicate that the GATA4 gene closely resembles the other GATA family members in terms of gene structure where alternative first exon usage appears to be an important mechanism for regulating its tissue- and cell-specific expression

Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism

correction de l'article correspondant à la notice https://prodinra.inra.fr/record/425677International audienceConcern has been raised over increased male reproductive disorders in the Western world, and the disruption of male endocrinology has been suggested to play a central role. Several studies have shown that mild analgesics exposure during fetal life is associated with antiandrogenic effects and congenital malformations, but the effects on the adult man remain largely unknown. Through a clinical trial with young men exposed to ibuprofen, we show that the analgesic resulted in the clinical condition named "compensated hypogonadism," a condition prevalent among elderly men and associated with reproductive and physical disorders. In the men, luteinizing hormone (LH) and ibuprofen plasma levels were positively correlated, and the testosterone/LH ratio decreased. Using adult testis explants exposed or not exposed to ibuprofen, we demonstrate that the endocrine capabilities from testicular Leydig and Sertoli cells, including testosterone production, were suppressed through transcriptional repression. This effect was also observed in a human steroidogenic cell line. Our data demonstrate that ibuprofen alters the endocrine system via selective transcriptional repression in the human testes, thereby inducing compensated hypogonadism

Parallel assessment of the effects of bisphenol A and several of its analogs on the adult human testis

International audienceStudy question - Are bisphenol A (BPA) and BPA analogs (BPA-A) safe for male human reproductive function? Summary answer - The endocrine function of human testes explants [assessed by measuring testosterone and insulin-like factor 3 (INSL3)] was impacted by exposure of the human adult testis explants to BPA/BPA-A. What is known already - The few epidemiologic studies performed suggest that bisphenols have potential endocrine disruptive properties, but they did not identify clear and direct patterns of endocrine disruption. Study design, size, duration - Adult human testis explants in culture were exposed to BPA and the analogs bisphenol F (BPF), bisphenol S (BPS), bisphenol E (BPE), bisphenol B (BPB) and bisphenol A diglycidyl ether (BADGE) at 10-9-10-5 M for 24 or 48 h. Participants/materials, setting, methods - Human adult testes were obtained from prostate cancer patients who had no hormone therapy, or from multiorgan donors. After ex vivo exposure to the investigated bisphenols, the measured outcomes were related to histopathology (gross morphology and germ cell viability determined by anti-caspase three immunohistochemistry), and the levels of testosterone, INSL3 and inhibin B were measured using immunoassays. The levels of mRNA encoding key enzymes of bisphenol biotransformation were investigated by quantitative PCR: UGT2B15 UDP (glucuronosyltransferase two family, polypeptide B15), GUSB (glucuronidase beta), SULT1A1 and 3 (sulfotransferase family 1 A member 1 and 3) and STS (steroid sulfatase). Main results and the role of chance - A significant dose-dependent inhibition was found between testosterone levels measured in the culture medium and concentrations of BPA (P = 0.00778 at 24 h and P = 0.0291 at 48 h), BPE (P = 0.039) and BPF (P = 0.00663). The observed BPA and BPA-A-induced inhibition of testosterone production varied according to duration of exposure and BPA/BPA-A concentrations. BPA (10-9 M; P < 0.05), BPB (10-9 M; P < 0.05), BPS (10-9 and 10-8 M; P < 0.05) and BADGE (10-5 M; P < 0.05) increased Leydig cell INSL3 production. By contrast, BPE dose dependently inhibited INSL3 (P = 0.0372). Conversely, Sertoli cell function (inhibin B) and germ cell viability were not significantly affected by either bisphenols. Large scale data - N/A. Limitations, reasons for caution - Environmental compounds cannot be deliberately administered to men, justifying the use of an ex vivo approach. A relatively low number of testes samples were available for analysis (n = 3, except for testosterone secretion with n = 5). The active concentrations of BPA and BPA-A used in the study were higher than those found in human biological fluids. Wider implications of the findings - Under our experimental conditions, direct exposure to BPA or BPA-A can result in endocrine disturbance in the adult human testis. Study funding/competing interest(s) - This study was funded by Inserm (Institut National de la Santé et de la Recherche Médicale), EHESP-School of Public Health, University of Rennes1, by grants from the Agence Nationale de la Recherche (ANR; grant#ANR-13-CESA-0012-03 NEWPLAST) and Agence Nationale de Sécurité Sanitaire de l'Alimentation, de l'Environnement et du Travail (ANSES; grant#EST-2010/2/046 (BPATESTIS)). All authors declare they have no current or potential competing financial interests

Integrated metabolomic, lipidomic and steroidomic profiling for revealing signatures and markers of effect induced by bisphenols exposure on human testicular function

International audienceThe Newplast research project (ANR-13-CESA-0012-01) focuses on substitutes and derivatives of bisphenol A (BPA) which are used in the manufacture of polycarbonate and epoxy resins, including food contact materials. Its global objective is to generate data and knowledge as regards (i) their biotransformation and biological impact on the human hepatic and reproductive functions, (ii) their modes of actions at molecular level through ligand-receptor binding / transactivation mechanisms and (iii) human external and internal exposure assessment. The effect of BPA and related substitutes (BPS and BPF) on testicular function was assessed on fetal (FEGA) and adult (TEXAS) models using an integrated metabolomic, lipidomic and steroidomic profiling approach. Three complementary workflows were then combined to generate a unique set of biological signatures as a support for markers of effect discovery. A rationalized sample preparation permitted to fractionate each characterized sample into one polar fraction for RPLC-ESI(+/-)-HRMS metabolomic profiling, and one apolar phase for RPLC-ESI(+/-)-HRMS lipidomic and GC-EI-MS/MS steroidomic profiling. Moreover a comprehensive characterization from both culture medium (exo-metabolome) and testicular tissue (endo-metabolome) was achieved. All together, obtained results give an extended picture of biological disruptions induced by BPA and two main substitutes (BPS and BPF) on human testicular target, including dose-responses and mixture effects. A set of annotated and particularly affected metabolites was revealed from each investigated metabolome sub-component

Anatomic and functional mapping of human uterine innervation

International audienceOBJECTIVE: To better understand the physiology of pain in pelvic pain pathological conditions, such as endometriosis, in which alterations of uterine innervation have been highlighted, we performed an anatomic and functional mapping of the macro- and microinnervation of the human uterus. Our aim was to provide a 3-dimensional reconstruction model of uterine innervation. DESIGN: This was an experimental study. We dissected the pelvises of 4 human female fetuses into serial sections, and treated them with hematoxylin and eosin staining before immunostaining. SETTING: Academic Research Unit. PATIENTS: None. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Detection of nerves (S100 +) and characterization of the types of nerves. The slices obtained were aligned to construct a 3-dimensional model. RESULTS: A 3-dimensional model of uterine innervation was constructed. The nerve fibers appeared to have a centripetal path from the uterine serosa to the endometrium. Within the myometrium, innervation was dense. Endometrial innervation was sparse but present in the functional layer of the endometrium. Overall innervation was richest in the supravaginal cervix and rarer in the body of the uterus. Innervation was rich particularly laterally to the cervix next to the parametrium and paracervix. Four types of nerve fibers were identified: autonomic sympathetic (TH+), parasympathetic (VIP+), and sensitive (NPY+, CGRP1+ and VIP+). They were found in the 3 portions and the 3 layers of the uterus. CONCLUSIONS: We constructed a 3-dimensional model of the human uterine innervation. This model could provide a solid base for studying uterine innervation in pathologic situations, in order to find new therapeutic approaches

An investigation of the endocrine-disruptive effects of bisphenol a in human and rat fetal testes.

International audienc