Éditeur(s) : HAL CCSD
Résumé : International audience
Background: We examined the association between exposure during pregnancy to trihalomethanes, the most common water disinfection by-products, and birth outcomes in a European cohort study (Health Impacts of Long-Term Exposure to Disinfection By-Products in Drinking Water). We took into account exposure through different water uses, measures of water toxicity, and genetic susceptibility. Methods: We enrolled 14,005 mothers (2002-2010) and their children from France, Greece, Lithuania, Spain, and the UK. Information on lifestyle- and water-related activities was recorded. We ascertained residential concentrations of trihalomethanes through regulatory records and ad hoc sampling campaigns and estimated route-specific trihalomethane uptake by trimester and for whole pregnancy. We examined single nucleotide polymorphisms and copy number variants in disinfection by-product metabolizing genes in nested case-control studies. Results: Average levels of trihalomethanes ranged from around 10 μg/L to above the regulatory limits in the EU of 100 μg/L between centers. There was no association between birth weight and total trihalomethane exposure during pregnancy (β = 2.2 g in birth weight per 10 μg/L of trihalomethane, 95% confidence interval = 3.3, 7.6). Birth weight was not associated with exposure through different routes or with specific trihalomethane species. Exposure to trihalomethanes was not associated with low birth weight (odds ratio [OR] per 10 μg/L = 1.02, 95% confidence interval = 0.95, 1.10), small-for-gestational age (OR = 0.99, 0.94, 1.03) and preterm births (OR = 0.98, 0.9, 1.05). We found no gene-environment interactions for mother or child polymorphisms in relation to preterm birth or small-for-gestational age. Conclusions: In this large European study, we found no association between birth outcomes and trihalomethane exposures during pregnancy in the total population or in potentially genetically susceptible subgroups. © 2016 Wolters Kluwer Health, Inc.
Epidemiology

hal-01392115
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01392115
DOI : 10.1097/EDE.0000000000000544
PUBMED : 27468006

Éditeur(s) : HAL CCSD Endocrine Society
Résumé : International audience
Transcriptional regulation by the estrogen receptor-alpha(ER) has been investigated mainly in breast cancer cell lines, but estrogens such as 17 beta-estradiol (E2) exert numerous extrareproductive effects, particularly in the liver, where E2 exhibits both protective metabolic and deleterious thrombotic actions. To analyze the direct and early transcriptional effects of estrogens in the liver, we determined the E2-sensitive transcriptome and ER cistrome in mice after acute administration of E2 or placebo. These analyses revealed the early induction of genes involved in lipid metabolism, which fits with the crucial role of ER in the prevention of liver steatosis. Characterization of the chromatin state of ER binding sites (BSs) in mice expressing or not ER demonstrated that ER is not required per se for the establishment and/or maintenance of chromatin modifications at the majority of its BSs. This is presumably a consequence of a strong overlap between ER and hepatocyte nuclear factor 4 alpha BSs. In contrast, 40% of the BSs of the pioneer factor forkhead box protein a (Foxa2) were dependent upon ER expression, and ER expression also affected the distribution of nucleosomes harboring dimethylated lysine 4 of Histone H3 around Foxa2 BSs. We finally show that, in addition to a network of liver-specific transcription factors including CCAAT/enhancer-binding protein and hepatocyte nuclear factor 4 alpha, ER might be required for proper Foxa2 function in this tissue.
ISSN: 0888-8809

hal-01357623
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01357623
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01357623/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01357623/file/Changes%20in%20gene%20expression%201%20and%20Estrogen%20Receptor_accepted.pdf
DOI : 10.1210/me.2015-1311

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Archives of Cardiovascular Diseases Supplements
Strasbourg, France

hal-01118035
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118035
DOI : 10.1016/S1878-6480(14)71283-2

Éditeur(s) : HAL CCSD IWA Publishing
Résumé : International audience
EISSN: 1605-3974

hal-01128014
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01128014
DOI : 10.2166/aqua.2013.017

Éditeur(s) : HAL CCSD
Résumé : International audience
Women who drink light-to-moderately during pregnancy have been observed to have lower risk of unfavourable pregnancy outcomes than abstainers. This has been suggested to be a result of bias. In a pooled sample, including 193 747 live-born singletons from nine European cohorts, we examined the associations between light-to-moderate drinking and preterm birth, birth weight, and small-for-gestational age in term born children (term SGA). To address potential sources of bias, we compared the associations from the total sample with a sub-sample restricted to first-time pregnant women who conceived within six months of trying, and examined whether the associations varied across calendar time. In the total sample, drinking up to around six drinks per week as compared to abstaining was associated with lower risk of preterm birth, whereas no significant associations were found for birth weight or term SGA. Drinking six or more drinks per week was associated with lower birth weight and higher risk of term SGA, but no increased risk of preterm birth. The analyses restricted to women without reproductive experience revealed similar results. Before 2000 approximately half of pregnant women drank alcohol. This decreased to 39% in 2000–2004, and 14% in 2005–2011. Before 2000, every additional drink was associated with reduced mean birth weight, whereas in 2005–2011, the mean birth weight increased with increasing intake. The period-specific associations between low-to-moderate drinking and birth weight, which also were observed for term SGA, are indicative of bias. It is impossible to distinguish if the bias is attributable to unmeasured confounding, which change over time or cohort heterogeneity. © 2017, Springer Science+Business Media B.V.
ISSN: 03932990

hal-01647159
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647159
DOI : 10.1007/s10654-017-0323-2
PUBMED : 29027084

Éditeur(s) : HAL CCSD American Chemical Society
Résumé : International audience
The HIWATE (Health Impacts of long-term exposure to disinfection byproducts in drinking WATEr) project was a systematic analysis that combined the epidemiology on adverse pregnancy outcomes and other health effects with long-term exposure to low levels of drinking water disinfection byproducts (DBPs) in the European Union. The present study focused on the relationship of the occurrence and concentration of DBPs with in vitro mammalian cell toxicity. Eleven drinking water samples were collected from five European countries. Each sampling location corresponded with an epidemiological study for the HIWATE program. Over 90 DBPs were identified; the range in the number of DBPs and their levels reflected the diverse collection sites, different disinfection processes, and the different characteristics of the source waters. For each sampling site, chronic mammalian cell cytotoxicity correlated highly with the numbers of DBPs identified and the levels of DBP chemical classes. Although there was a clear difference in the genotoxic responses among the drinking waters, these data did not correlate as well with the chemical analyses. Thus, the agents responsible for the genomic DNA damage observed in the HIWATE samples may be due to unresolved associations of combinations of identified DBPs, unknown emerging DBPs that were not identified, or other toxic water contaminants. This study represents the first to integrate quantitative in vitro toxicological data with analytical chemistry and human epidemiologic outcomes for drinking water DBPs.
ISSN: 0013-936X

hal-00875923
https://hal.archives-ouvertes.fr/hal-00875923
DOI : 10.1021/es3024226
PUBMED : 22958121

Éditeur(s) : HAL CCSD Awwa American Water Works Association
Résumé : International audience
A three-year study was conducted on the occurrence of disinfection by-products (DBPs) - trihalomethanes (THMs), haloacetic acids (HAAs), and haloacetonitriles - in drinking water of regions of Europe where epidemiology studies were being carried out. Thirteen systems in six countries (i.e., Italy, France, Greece, Lithuania, Spain, United Kingdom) were sampled. Typically chlorinated DBPs dominated. However, in most of Catalonia (Spain) and in Heraklion (Greece), brominated DBPs dominated. The degree of bromine incorporation into the DBP classes was in general similar among them. This is important, as brominated DBPs are a greater health concern. In parts of Catalonia, the reported levels of tribromoacetic acid were higher than in other parts of the world. In some regions, the levels of HAAs tended to be peaked in concentration in a different time period than when the levels of THMs peaked. In most epidemiology studies, THMs are used as a surrogate for other halogenated DBPs. This study provides exposure assessment information for epidemiology studies. © 2016 American Water Works Association.
ISSN: 0003-150X

hal-01406069
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01406069
DOI : 10.5942/jawwa.2016.108.0152

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
A nested case-control association study was designed to investigate the influence of maternal and fetal copy number variants (CNVs) on reproductive outcomes. Genotypes of ten CNVs encompassing GST and CYP genes were assessed. Significant associations were only found for child CNV genotypes. In particular, the child GSTM1 insertion allele was associated with prematurity protection (odds ratio, 95% CI: 0.67, 0.51-0.89; P < 0.01), whereas the child GSTT2B insertion allele was associated with an increased risk of being small for gestational age (odds ratio, 95% CI: 1.33, 1.07-1.67; P = 0.01). The study highlights the role of the fetal genome in prenatal development and also the need to analyse CNVs in a systematic manner.
ISSN: 1470-0328

hal-00875955
https://hal.archives-ouvertes.fr/hal-00875955
DOI : 10.1111/j.1471-0528.2012.03400.x
PUBMED : 22676722

Éditeur(s) : HAL CCSD Oxford University Press
Résumé : International audience
The BioMart Community Portal (www.biomart.org) is a community-driven effort to provide a unified interface to biomedical databases that are distributed worldwide. The portal provides access to numerous database projects supported by 30 scientific organizations. It includes over 800 different biological datasets spanning genomics, proteomics, model organisms, cancer data, ontology information and more. All resources available through the portal are independently administered and funded by their host organizations. The BioMart data federation technology provides a unified interface to all the available data. The latest version of the portal comes with many new databases that have been created by our ever-growing community. It also comes with better support and extensibility for data analysis and visualization tools. A new addition to our toolbox, the enrichment analysis tool is now accessible through graphical and web service interface. The BioMart community portal averages over one million requests per day. Building on this level of service and the wealth of information that has become available, the BioMart Community Portal has introduced a new, more scalable and cheaper alternative to the large data stores maintained by specialized organizations.
ISSN: 0305-1048

hal-01146849
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146849
DOI : 10.1093/nar/gkv350
PUBMED : 25897122

Éditeur(s) : HAL CCSD Presses université de Laval
Résumé : International audience
This article aims to specify the challenges related to adapting the Disability Creation Process (DCP) model to the experience of chronic disease, specifically Human immunodeficiency virus (HIV). In this perspective, a conceptual clarification is proposed because the DCP is mainly used to study populations in situations of disability due to motor, sensory, mental or behavioral disabilities. However, this model seems to be able to adequately read the specific experience of HIV, and help to understand differently life trajec-tories of people living with HIV (PLHIV). Indeed, HIV infection, despite its status as a "chronic disease", continues to contribute to the risk of social isolation. Body modifications induced by the disease or its treatment has an impact on how others view PLHIV. They expose the visibility of HIV status and, ultimately, the fear of social exclusion. In this respect, the analysis of the DCP may allow us to understand the varia-tions in the quality of social participation and identify the phases of vulnerability by focusing on body image in particular induced by the infection or treatments. This approach provides the opportunity for new insight into the influence of social environments (particularly health management or community support) with re-gards to the lifestyle and the daily experiences of socially disadvantaged people.
Cet article tente de spécifier les enjeux d’une adaptation du modèle du Processus de production du handicap (PPH) au vécu de la maladie chronique, et plus spécifiquement du virus de l’immunodéfi-cience humaine (VIH). Dans cette perspective, un éclaircissement conceptuel est proposé, car le PPH a principalement été utilisé pour étudier les populations vivant des situations de handicap liées à des incapa-cités motrices, sensorielles, intellectuelles ou comportementales. Ce modèle semble toutefois en mesure de renouveler la lecture de l’expérience spécifique du VIH, et d’aider à saisir autrement les trajectoires de vie des personnes vivant avec le VIH (PVVIH). En effet, l’infection au VIH, malgré son statut de « maladie chronique », demeure associée à un risque d’isolement social. Les modifications corporelles induites par la maladie ou par son traitement confronte les PVVIH au regard de l’autre. Elles exposent à la visibilité du statut sérologique et, in fine, à la peur de l’exclusion sociale. Dans ce cadre, l’analyse du Processus de production du handicap peut permettre de comprendre les variations de la qualité de la participation sociale et d’identifier les phases de vulnérabilité en s’intéressant notamment au rapport au corps induit par l’infection et les traitements. Cette approche offre l’opportunité d’un nouvel éclairage sur le poids des envi-ronnements sociaux (notamment des dispositifs de prises en charge sanitaire ou d’accompagnement communautaire) sur les habitudes de vie et l’expérience quotidienne d’un public fragilisé socialement.
ISSN: 1499-5549

hal-01681423
https://hal.archives-ouvertes.fr/hal-01681423

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The interpretation of high-resolution 2D marine seismic profiles together with the analysis of sea-bottom cores allowed a stratigraphic and structural framework of the Provence continental shelf to be proposed. The integration of onshore and offshore stratigraphy, structure and geomorphology provided new insights into Messinian paleotopography and paleohydrography. A geological map of the offshore Provence continental shelf, isobath map of the base Plio-Quaternary surface are presented for the first time in this area. The base Plio-Quaternary surface is a polyphased unconformity that is composed of deep canyons developed by fluvial erosion during the Messinian event, and wave-cut surfaces formed during post-Messinian transgressions. The study evidenced a deep, E-W-trending canyon (Bandol canyon) connected to the head of the Cassidaigne canyon, and filled with up to 600 m-thick Plio-Quaternary deposits. The development of canyons on the Provence margin during the Messinian event was dominantly controlled by the lithology and structure of pre-Messinian formations. A map of the Messinian paleo-drainage network is proposed to explain the presence of deep canyons in the Eastern area and the lack of incision in the Western area. An underground karst drainage scheme is proposed, linked with the current submarine Port-Miou spring.
ISSN: 0264-8172

insu-01009592
https://hal-insu.archives-ouvertes.fr/insu-01009592
https://hal-insu.archives-ouvertes.fr/insu-01009592/document
https://hal-insu.archives-ouvertes.fr/insu-01009592/file/Mar-Pet-Tassy.pdf
DOI : 10.1016/j.marpetgeo.2014.05.001

Éditeur(s) : HAL CCSD Wiley Open Access
Résumé : International audience
Estetrol (E4) is a natural estrogen with a long half-life produced only by the human fetal liver during pregnancy. The crystal structures of the estrogen receptor α (ERα) ligand-binding domain bound to 17β-estradiol (E2) and E4 are very similar, as well as their capacity to activate the two activation functions AF-1 and AF-2 and to recruit the coactivator SRC3. In vivo administration of high doses of E4 stimulated uterine gene expression, epithelial proliferation, and prevented atheroma, three recognized nuclear ERα actions. However, E4 failed to promote endothelial NO synthase activation and acceleration of endothelial healing, two processes clearly dependent on membrane-initiated steroid signaling (MISS). Furthermore, E4 antagonized E2 MISS-dependent effects in endothelium but also in MCF-7 breast cancer cell line. This profile of ERα activation by E4, uncoupling nuclear and membrane activation, characterizes E4 as a selective ER modulator which could have medical applications that should now be considered further.
ISSN: 1757-4676

hal-01118028
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118028
PUBMED : 25214462
PUBMEDCENTRAL : PMC4287935
DOI : 10.15252/emmm.201404112