Transcriptomic analysis of human placenta in intrauterine growth restriction.
BACKGROUND
Intrauterine growth restriction (IUGR) is a frequent complication of pregnancy defined as a restriction of fetal growth. The objective of this work was to improve the knowledge on the pathophysiology of IUGR using a genome-wide method of expression analysis.


METHODS
We analyzed differentially expressed genes in pooled placental tissues from vascular IUGR (four pools of three placentas) and normal pregnancies (four pools of three placentas) using a long nucleotide microarray platform (Nimblegen). We first did a global bioinformatics analysis based only on P value without any a priori. We secondly focused on "target" genes among the most modified ones. Finally, reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed on an extended panel of tissue samples (n = 62) on selected "target".


RESULTS
We identified 636 modified genes among which 206 were upregulated (1.5 and higher; P < 0.05). Groups of patients were classified unambiguously. Genes involved in mitochondrial function and oxidative phosphorylation were decreased affecting three out of five complexes of the respiratory chain of the mitochondria, and thus energy production and metabolism. Among the most induced genes, we identified LEP, IGFBP1, and RBP4.


CONCLUSIONS
Complementary studies on the role and function of LEP, IGFBP1, and RBP4 in IUGR pathophysiology and also in fetal programming remain necessary.
1] Inserm U1016, Institut Cochin, Paris, France [2] Cnrs UMR8104, Institut Cochin, Paris, France [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France [4] Réanimation et Médecine Néonatales, CHU Cochin, APHP, Paris, France.
Doriane
D
Madeleneau
Laboratoire de Biologie Moléculaire, Hôpital la Conception, AP-HM, Marseille, France.
Christophe
C
Buffat
1] Inserm U1016, Institut Cochin, Paris, France [2] Cnrs UMR8104, Institut Cochin, Paris, France [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Françoise
F
Mondon
1] Inserm U1016, Institut Cochin, Paris, France [2] Cnrs UMR8104, Institut Cochin, Paris, France [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France [4] Réanimation et Médecine Néonatales, CHU Angers, Angers, France.
Hélène
H
Grimault
1] Inserm U1016, Institut Cochin, Paris, France [2] Cnrs UMR8104, Institut Cochin, Paris, France [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France [4] Réanimation et Médecine Néonatales, CHU Necker Enfants Malades, APHP, Paris, France.
Virginie
V
Rigourd
Gynécologie Obstétricale, CHU Cochin, APHP, Paris, France.
Vassilis
V
Tsatsaris
1] Inserm U1016, Institut Cochin, Paris, France [2] Cnrs UMR8104, Institut Cochin, Paris, France [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Franck
F
Letourneur
1] Inserm U1016, Institut Cochin, Paris, France [2] Cnrs UMR8104, Institut Cochin, Paris, France [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Daniel
D
Vaiman
1] Inserm U1016, Institut Cochin, Paris, France [2] Cnrs UMR8104, Institut Cochin, Paris, France [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Sandrine
S
Barbaux
1] Inserm U1016, Institut Cochin, Paris, France [2] Cnrs UMR8104, Institut Cochin, Paris, France [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France [4] Réanimation et Médecine Néonatales, CHU Angers, Angers, France.
Géraldine
G
Gascoin
D019295:Computational Biology; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics* / Q000503:physiopathology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D063990:Gene Ontology; D006801:Humans; D046228:Microarray Analysis; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction