A hierarchical analysis of transcriptome alterations in intrauterine growth restriction (IUGR) reveals common pathophysiological pathways in mammals.

Détails

ID Serval
serval:BIB_40F1544F01F0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A hierarchical analysis of transcriptome alterations in intrauterine growth restriction (IUGR) reveals common pathophysiological pathways in mammals.
Périodique
Journal of Pathology
Auteur⸱e⸱s
Buffat C., Mondon F., Rigourd V., Boubred F., Bessières B., Fayol L., Feuerstein J.M., Gamerre M., Jammes H., Rebourcet R., Miralles F., Courbières B., Basire A., Dignat-Georges F., Carbonne B., Simeoni U., Vaiman D.
ISSN
0022-3417 (Print)
ISSN-L
0022-3417
Statut éditorial
Publié
Date de publication
2007
Peer-reviewed
Oui
Volume
213
Numéro
3
Pages
337-346
Langue
anglais
Notes
Publication types: Journal Article Publication Status: ppublish
Résumé
Intra-uterine growth restriction (IUGR) is a frequent disease, affecting up to 10% of human pregnancies and responsible for increased perinatal morbidity and mortality. Moreover, low birth weight is an important cause of the metabolic syndrome in the adult. Protein depletion during the gestation of rat females has been widely used as a model for human IUGR. By transcriptome analysis of control and protein-deprived rat placentas, we were able to identify 2543 transcripts modified more than 2.5 fold (1347 induced and 1196 repressed). Automatic functional classification enabled us to identify clusters of induced genes affecting chromosome structure, transcription, intracellular transport, protein modifications and apoptosis. In particular, we suggest the existence of a complex balance regulating apoptosis. Among repressed genes, we noted several groups of genes involved in immunity, signalling and degradation of noxious chemicals. These observations suggest that IUGR placentas have a decreased resistance to external aggression. The promoters of the most induced and most repressed genes were contrasted for their composition in putative transcription factor binding sites. There was an over-representation of Zn finger (ZNF) proteins and Pdx1 (pancreatic and duodenal homeobox protein 1) putative binding sites. Consistently, Pdx1 and a high proportion of ZNF genes were induced at the transcriptional level. A similar analysis of ZNF promoters showed an increased presence of putative binding sites for the Tata box binding protein (Tbp). Consistently again, we showed that the Tbp and TBP-associated factors (Tafs) were up-regulated in IUGR placentas. Also, samples of human IUGR and control placentas showed that human orthologous ZNFs and PDX1 were transcriptionally induced, especially in non-vascular IUGR. Immunohistochemistry revealed increased expression of PDX1 in IUGR human placentas. In conclusion, our approach permitted the proposition of hypotheses on a hierarchy of gene inductions/repressions leading to massive transcriptional alterations in the IUGR placenta, in humans and in rodents.
Mots-clé
Adult, Analysis of Variance, Animals, Case-Control Studies, Cluster Analysis, Female, Fetal Growth Retardation/genetics, Fetal Growth Retardation/metabolism, Gene Expression Profiling, Humans, Immunohistochemistry, Infant, Newborn, Models, Animal, Oligonucleotide Array Sequence Analysis, Placenta/metabolism, Pregnancy, Principal Component Analysis, Promoter Regions, Genetic, Rats, Rats, Sprague-Dawley, Reverse Transcriptase Polymerase Chain Reaction, Statistics, Nonparametric, Transcription, Genetic
Pubmed
Création de la notice
22/02/2015 9:02
Dernière modification de la notice
20/08/2019 13:40
Données d'usage