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To identify changes in gene expression associated with preterm labor (PTL) induced by either infection or ovariectomy (a progesterone withdrawal model).
Pregnant mice (14 days of gestation) were allocated to: 1) intrauterine injection of heat-inactivated E. coli; 2) media alone; 3) ovariectomy; or 4) sham operation. Samples of uterine tissue were harvested at pre-defined time points and at parturition. The uterine transcriptome was studied using Affymetrix mgu74av2 arrays.
1) Infection- and ovariectomy-induced PTL exhibited 1010 and 269 expression changes (P ≤ 0.01), respectively; 2) Gene Ontology analyses identified overrepresentation of genes involved in fatty-acid and carboxylic-acid metabolism in infection-induced PTL (P ≤ 0.0037 and P ≤ 0.05); 3) Gene expression changes in the arachidonate metabolism pathway were globally associated with both infection-induced PTL (P ≤ 0.00035) and ovariectomy-induced PTL (P ≤ 0.00036); 4) Importantly, ovariectomy-induced PTL had increased expression of genes involved in lipoxin, leukotriene, 5-HETE and lecithin synthesis (Alox15 +3.0-fold, Lta4h +1.2-fold, Pla2g4 +1.8-fold, Prdx6 +1.2-fold, respectively), whereas infection-induced PTL had slightly decreased, or unchanged, expression in these same genes; and 5) Infection-induced PTL increased the expression of genes involved in prostaglandin synthesis (Ptgs +36.5-fold, Ptges +16-fold) and 12-HPETE synthesis (Alox12 +1.7-fold). Ovariectomy-induced PTL exhibited different changes in the magnitude in the same pathway branches (Ptgs +6.8-fold, Ptges unchanged, Alox12 +4.0-fold).
Ovariectomy-induced PTL differs from infection-induced PTL by the increased expression of genes involved in lipoxin, leukotriene, 5-HETE and lecithin synthesis.