title: Hypoxia-activated genes from early placenta are elevated in preeclampsia, but not in Intra-Uterine Growth Retardation.
abstract: BACKGROUND
  As a first step to explore the possible relationships existing between the effects of low oxygen pressure in the first trimester placenta and placental pathologies developing from mid-gestation, two subtracted libraries totaling 2304 cDNA clones were constructed. For achieving this, two reciprocal suppressive/subtractive hybridization procedures (SSH) were applied to early (11 weeks) human placental villi after incubation either in normoxic or in hypoxic conditions. The clones from both libraries (1440 hypoxia-specific and 864 normoxia-specific) were spotted on nylon macroarrays. Complex cDNAs probes prepared from placental villi (either from early pregnancy, after hypoxic or normoxic culture conditions, or near term for controls or pathological placentas) were hybridized to the membranes.
  
  
  RESULTS
  Three hundred and fifty nine clones presenting a hybridization signal above the background were sequenced and shown to correspond to 276 different genes. Nine of these genes are mitochondrial, while 267 are nuclear. Specific expression profiles characteristic of preeclampsia (PE) could be identified, as well as profiles specific of Intra-Uterine Growth Retardation (IUGR). Focusing on the chromosomal distribution of the fraction of genes that responded in at least one hybridization experiment, we could observe a highly significant chromosomal clustering of 54 genes into 8 chromosomal regions, four of which containing imprinted genes. Comparative mapping data indicate that these imprinted clusters are maintained in synteny in mice, and apparently in cattle and pigs, suggesting that the maintenance of such syntenies is requested for achieving a normal placental physiology in eutherian mammals.
  
  
  CONCLUSIONS
  We could demonstrate that genes induced in PE were also genes highly expressed under hypoxic conditions (P = 5 x 10(-5)), which was not the case for isolated IUGR. Highly expressed placental genes may be in syntenies conserved interspecifically, suggesting that the maintenance of such clusters is requested for achieving a normal placental physiology in eutherian mammals.
authors.affiliation: Génétique et Epigénétique des Pathologies Placentaires, GEPP, U709 INSERM-Université René Descartes, Institut Alfred Jost, Pavillon Baudelocque, Hôpital Cochin, 75014, Paris, France. vaiman@cochin.inserm.fr
authors.forename: Daniel
authors.initials: D
authors.lastname: Vaiman
authors.forename: Françoise
authors.initials: F
authors.lastname: Mondon
authors.forename: Alexandra
authors.initials: A
authors.lastname: Garcès-Duran
authors.forename: Thérèse-Marie
authors.initials: TM
authors.lastname: Mignot
authors.forename: Brigitte
authors.initials: B
authors.lastname: Robert
authors.forename: Régis
authors.initials: R
authors.lastname: Rebourcet
authors.forename: Hélène
authors.initials: H
authors.lastname: Jammes
authors.forename: Sonia T
authors.initials: ST
authors.lastname: Chelbi
authors.forename: Frédérique
authors.initials: F
authors.lastname: Quetin
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Marceau
authors.forename: Vincent
authors.initials: V
authors.lastname: Sapin
authors.forename: François
authors.initials: F
authors.lastname: Piumi
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Danan
authors.forename: Virginie
authors.initials: V
authors.lastname: Rigourd
authors.forename: Bruno
authors.initials: B
authors.lastname: Carbonne
authors.forename: Françoise
authors.initials: F
authors.lastname: Ferré
mesh_terms: D000328:Adult; D000818:Animals; D002875:Chromosomes / Q000378:metabolism / Q000648:ultrastructure; D016000:Cluster Analysis; D003582:Cytogenetics; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D015723:Gene Library; D006801:Humans; D000860:Hypoxia; D007700:Kinetics; D008928:Mitochondria / Q000378:metabolism; D008957:Models, Genetic; D015233:Models, Statistical; D005810:Multigene Family; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010920:Placenta / Q000378:metabolism*; D011061:Poly A / Q000378:metabolism; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012313:RNA / Q000378:metabolism; D013552:Swine
chemical_list: D018076:DNA, Complementary; D011061:Poly A; D012313:RNA