Contributors: Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB); Centre Hospitalier Universitaire CHU Grenoble (CHUGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA); Institut Cochin (IC UM3 (UMR 8104 / U1016)); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Institut de Biologie François JACOB (JACOB); Direction de Recherche Fondamentale (CEA) (DRF (CEA)); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA); Harvard T.H. Chan School of Public Health; École des Hautes Études en Santé Publique EHESP (EHESP); Institut de recherche en santé, environnement et travail (Irset); Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique EHESP (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ); Centre for Research in Epidemiology and Statistics; Conservatoire National des Arts et Métiers CNAM (CNAM); HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); French National Cancer Institute (INCa); French Institute for Public Health Research (IreSP) INCa_13641; Fondation de France 2012-00031593, 2012-00031617; French Ministry of Health (DGS); French Ministry of Research, Inserm Bone and Joint Diseases National Research (PRO-A); Human Nutrition National Research Programs, Paris-Sud University; Nestle; French National Institute for Population Health Surveillance (InVS); French National Institute for Health Education (INPES); European Union; Diabetes National Research Program (French Association of Diabetic Patients (AFD)); ANSES; Mutuelle Generale de l'Education Nationale (MGEN); French National Agency for Food Security; Frenchspeaking Association for the Study of Diabetes and Metabolism (ALFEDIAM); Foundation for Medical Research (FRM); National Institute for Research in Public Health (IRESP: TGIR cohorte sante 2008 program); ANR-18-CE36-0005,ETAPE,Exposition prénatale au tabac et à la pollution atmosphérique et effets sur la santé respiratoire et le neurodévelopment de l'enfant: rôle de la méthylation placentaire(2018); ANR-13-CESA-0011,EPPAP,Effets de la Pollution Atmosphérique sur la fonction Placentaire et le développement Post-natal(2013)
نبذة مختصرة : International audience ; Background Maternal blood pressure levels reflect cardiovascular adaptation to pregnancy and proper maternal-fetal exchanges through the placenta and are very sensitive to numerous environmental stressors. Maternal hypertension during pregnancy has been associated with impaired placental functions and with an increased risk for children to suffer from cardiovascular and respiratory diseases later on. Investigating changes in placental DNA methylation levels and cell-type composition in association with maternal blood pressure could help elucidate its relationships with placental and fetal development. Methods Taking advantage of a large cohort of 666 participants, we investigated the association between epigenome-wide DNA methylation patterns in the placenta, measured using the Infinium HumanMethylation450 BeadChip, placental cell-type composition, estimated in silico, and repeated measurements of maternal steady and pulsatile blood pressure indicators during pregnancy. Results At the site-specific level, no significant association was found between maternal blood pressure and DNA methylation levels after correction for multiple testing (false discovery rate < 0.05), but 5 out of 24 previously found CpG associations were replicated (p-value < 0.05). At the regional level, our analyses highlighted 64 differentially methylated regions significantly associated with at least one blood pressure component, including 35 regions associated with mean arterial pressure levels during late pregnancy. These regions were found enriched for genes implicated in lung development and diseases. Further mediation analyses show that a significant part of the association between steady blood pressure-but not pulsatile pressure-and placental methylation can be explained by alterations in placental cell-type composition. In particular, elevated blood pressure levels are associated with a decrease in the ratio between mesenchymal stromal cells and syncytiotrophoblasts, even in the absence of preeclampsia. ...
_1.png)
Processing Request
No Comments.