Hypoxia-activated genes from early placenta are elevated in preeclampsia, but not in Intra-Uterine Growth Retardation.
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.
Vaiman
Daniel
D
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
Mondon
Françoise
F
Garcès-Duran
Alexandra
A
Mignot
Thérèse-Marie
TM
Robert
Brigitte
B
Rebourcet
Régis
R
Jammes
Hélène
H
Chelbi
Sonia T
ST
Quetin
Frédérique
F
Marceau
Geoffrey
G
Sapin
Vincent
V
Piumi
François
F
Danan
Jean-Louis
JL
Rigourd
Virginie
V
Carbonne
Bruno
B
Ferré
Françoise
F
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
D018076:DNA, Complementary; D011061:Poly A; D012313:RNA