Early pregnancy peripheral blood gene expression and risk of preterm delivery: a nested case control study

<p>Abstract</p> <p>Background</p> <p>Preterm delivery (PTD) is a significant public health problem associated with greater risk of mortality and morbidity in infants and mothers. Pathophysiologic processes that may lead to PTD start early in pregnancy. We investigated early pregnancy peripheral blood global gene expression and PTD risk.</p> <p>Methods</p> <p>As part of a prospective study, ribonucleic acid was extracted from blood samples (collected at 16 weeks gestational age) from 14 women who had PTD (cases) and 16 women who delivered at term (controls). Gene expressions were measured using the GeneChip^®Human Genome U133 Plus 2.0 Array. Student's T-test and fold change analysis were used to identify differentially expressed genes. We used hierarchical clustering and principle components analysis to characterize signature gene expression patterns among cases and controls. Pathway and promoter sequence analyses were used to investigate functions and functional relationships as well as regulatory regions of differentially expressed genes.</p> <p>Results</p> <p>A total of 209 genes, including potential candidate genes (e.g. PTGDS, prostaglandin D2 synthase 21 kDa), were differentially expressed. A set of these genes achieved accurate pre-diagnostic separation of cases and controls. These genes participate in functions related to immune system and inflammation, organ development, metabolism (lipid, carbohydrate and amino acid) and cell signaling. Binding sites of putative transcription factors such as EGR1 (early growth response 1), TFAP2A (transcription factor AP2A), Sp1 (specificity protein 1) and Sp3 (specificity protein 3) were over represented in promoter regions of differentially expressed genes. Real-time PCR confirmed microarray expression measurements of selected genes.</p> <p>Conclusions</p> <p>PTD is associated with maternal early pregnancy peripheral blood gene expression changes. Maternal early pregnancy peripheral blood gene expression patterns may be useful for better understanding of PTD pathophysiology and PTD risk prediction.</p

ROLE DES ISOFORMES DE PROTEINE KINASE C DANS LE CONTROLE DE LA CROISSANCE ET DE L'ACTIVITE CONTRACTILE DU MUSCLE UTERIN HUMAIN. REGULATION PAR L'ENDOTHELINE-1 ET ETUDE PHYSIOPATHOLOGIQUE

DANS LE MUSCLE LISSE UTERIN HUMAIN, DEUX PROPRIETES DE L'ENDOTHELINE-1 (ET-1) ONT ETE MISES EN EVIDENCE. SA CAPACITE A INDUIRE RAPIDEMENT DES CONTRACTIONS UTERINES IMPLIQUE UN ROLE DE CE PEPTIDE DANS LA PARTURITION HUMAINE, ET SON EFFET MITOGENE A PLUS LONG TERME SUR LES CELLULES MYOMETRIALES SUGGERE UN ROLE DE ET-1 DANS LE DEVELOPPEMENT NORMAL ET PHYSIOPATHOLOGIQUE DU MYOMETRE. AU COURS DE CE TRAVAIL, NOUS AVONS CARACTERISE, DANS LE MYOMETRE HUMAIN, LE SYSTEME ENZYMATIQUE PROTEINE KINASE C (PKC), SITUE AU CUR DE MECANISMES PHYSIOLOGIQUES (CONTRACTION, PROLIFERATION, DIFFERENCIATION) ET PHYSIOPATHOLOGIQUES (TUMORIGENESE). NOUS AVONS RECHERCHE SON IMPLICATION DANS LA TRANSDUCTION DU SIGNAL CONTRACTILE ET MITOGENE DE ET-1 DANS LE MYOMETRE NON GESTANT ET GESTANT. NOUS AVONS ETENDU NOTRE ETUDE AUX LEIOMYOMES UTERINS, QUI CONSTITUENT UN EXEMPLE DE DEVELOPPEMENT ANARCHIQUE DES CELLULES MYOMETRIALES. L'IDENTIFICATION DU SYSTEME PKC NOUS A PERMIS DE SOULIGNER QUE LES SIX ISOFORMES DE PKC (, 1, 2, , ET ) DETECTEES DANS LE MYOMETRE ISSU DE FEMMES NON GESTANTES SONT EGALEMENT PRESENTES DANS LE MYOMETRE DE FEMMES GESTANTES A TERME, DANS LES CELLULES MYOMETRIALES HUMAINES EN CULTURE, DANS LES LEIOMYOMES ET DANS LES CELLULES DE LEIOMYOMES HUMAINES. LA REGULATION DIFFERENTIELLE DES ISOFORMES DE PKC SOUS L'ACTION DE ET-1 DANS CES DIFFERENTES SITUATIONS SUGGERE QUE L'ACTIVITE CONTRACTILE ET LA CROISSANCE CELLULAIRE SONT, DANS LE MUSCLE LISSE UTERIN, REGULEES PAR DES ISOFORMES DE PKC SPECIFIQUES. DANS LE MYOMETRE DE FEMMES GESTANTES A TERME, NOUS AVONS MIS EN EVIDENCE UN ROLE DETERMINANT DES ISOFORMES DE PKC ET/OU DANS L'ACTION CONTRACTILE DE ET-1. DANS LES CELLULES MYOMETRIALES HUMAINES EN CULTURE, NOUS AVONS MONTRE QUE LA PKC EST RESPONSABLE DE L'EFFET MITOGENE DE ET-1. L'ACTION MITOGENE DE ET-1 DISPARAIT EN PRESENCE D'INHIBITEURS SPECIFIQUES DES PKC, APRES LEUR DEGRADATION PAR UN TRAITEMENT PROLONGE PAR LE PHORBOL 12, 13-DIBUTYRATE, ET PAR UNE INHIBITION SELECTIVE DE LA PKC PAR UN OLIGONUCLEOTIDE ANTISENS. DANS LES CELLULES DE LEIOMYOMES, ET-1 POTENTIALISE, VIA L'ACTIVATION DE LA PKC, L'EFFET MITOGENE DE FACTEURS DE CROISSANCE. CETTE ACTION INVERSE DE CELLE OBTENUE DANS LES CELLULES SAINES SUGGERE UN ROLE DE ET-1 DANS LE DEVELOPPEMENT DES TUMEURS BENIGNES DU MYOMETRE. L'ENSEMBLE DE NOS RESULTATS CONTRIBUENT A UNE MEILLEURE CONNAISSANCE DES MECANISMES DE REGULATION PAR ET-1, D'UNE PART DE L'ACTIVITE UTERINE, D'AUTRE PART DU DEVELOPPEMENT NORMAL ET PHYSIOPATHOLOGIQUE DU MYOMETRE HUMAIN. CET APPORT CONSTITUE UN PREALABLE A L'IDENTIFICATION DE CIBLES MOLECULAIRES POTENTIELLES, QUI PERMETTRAIENT DE PROPOSER DE NOUVELLES STRATEGIES THERAPEUTIQUES EFFICACES EN OBSTETRIQUE ET EN GYNECOLOGIE-ONCOLOGIE.PARIS-BIUSJ-Thèses (751052125) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Gene and protein expression in the myometrium in pregnancy and labor.

“Disclaimer. This is not the definitive version of record of this article. This manuscript has been accepted for publication in Reproduction, but the version presented here has not yet been copy edited, formatted or proofed. Consequently, the journal accepts no responsibility for any errors or omissions it may contain. The definitive version is available at http://dx.doi.org/10.1530/rep.1.00725. © 2006 Society for Reproduction and Fertility.”International audienceMicroarray technologies widen our comprehension of the major structural and metabolic transformations which affect the myometrium from the very beginning of pregnancy until parturition. The results are coherent with the mass of information which was accumulated previously, primarily on the basis of studies of selected critical factors. They highlight the activation of precise signaling pathways, some of which may have been previously under evaluated. The remodelling and maturation processes that the myometrium undergoes in pregnancy appear clearly as phenomena which last during the full course of gestation. Comparatively, the onset of labor is perhaps the phenomenon which remains the least well described by these methods of analysis. Nevertheless, genomic studies constitute a necessary first step of orientation and help establishing new links between the generic signaling pathways that are activated during the normal or pathological gestation. These studies also represent an indicative step that will have to be paralleled, in the future, with the results of the systematic proteomic analysis of the myometrium

Differential expression of the enzymatic system controlling synthesis, metabolism, and transport of PGF2 alpha in human fetal membranes

International audienceThe present study investigated the expression of genes and proteins associated with PGF2alpha biosynthesis, catabolism, and transport in matched amnion and choriodecidua of human term placenta. The concentration of PGF2alpha within fetal membranes depends on the balance between complex enzymatic systems responsible for, respectively, its synthesis-by prostaglandin-endoperoxide synthase 2 (PTGS2) and members of the aldo-keto reductase (AKR) family, AKR1C3 and AKR1B1-and its catabolic inactivation-through hydroxy-prostaglandin-dehydrogenase (HPGD). We observed that AKR1C3 shows equal basal expression (mRNA and protein) in choriodecidua and amnion but that AKR1B1 exhibits preferential expression in the choriodecidua. Expression of HPGD and solute carrier organic anion transporter family member 2A1 (SLCO2A1) was found primarily in the choriodecidua. We also evaluated whether an inflammatory environment induced by the gram-negative bacterial endotoxin lipopolysaccharide (LPS) affects expression of each candidate enzymes. The amnion responded to LPS with a small but significant decrease of AKR1B1 mRNA expression. In contrast, we found a significant increase in PTGS2 and AKR1C3 mRNA expression in choriodecidua after LPS challenge, but such regulation was confirmed only at protein levels for PTGS2 and not for AKR1C3. Our results suggest that the choriodecidua appears to be the main tissue, which expresses maximally all the components (synthesis, degradation, and transport) controlling PGF2alpha levels