Advertisement

Functional genomics reveals fundamental differences in the gene expression profile of infection-induced and progesterone withdrawal-induced preterm labor

      Objective

      To identify changes in gene expression associated with preterm labor (PTL) induced by either infection or ovariectomy (a progesterone withdrawal model).

      Study design

      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.

      Results

      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).

      Conclusion

      Ovariectomy-induced PTL differs from infection-induced PTL by the increased expression of genes involved in lipoxin, leukotriene, 5-HETE and lecithin synthesis.