Expression of myometrial activation and stimulation genes in a mouse model of preterm labor: Myometrial activation, stimulation, and preterm labor

Abstract

Myometrial contractions of labor result from an increase in myometrial activation and stimulation. Activation develops through the expression of contraction associated proteins (CAPs), including oxytocin receptors (OTR), connexin-43 (Cx-43), and prostaglandin F2α receptors (FP). Stimulation involves increases in contractile agonists including prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) that may result from increases in prostaglandin endoperoxide H synthase (PGHS)-2. A mouse model of preterm birth was used to study gene expression involved in myometrial activation and stimulation. To induce preterm birth, pregnant C57BL/6J mice were intubated with 6 g/kg ethanol on gestational day 16 and were killed every 6 h from treatment until birth. RIA was used to measure uterine PGE2 and PGF2α, while PGHS-2, OTR, Cx-43, and FP messenger RNA levels were measured by ribonuclease protection assay. Increases in CAP mRNA were associated with term and preterm birth. There were differences in stimulation effectors associated with preterm and term birth. Uterine PGF2α values were increased only at the time of term birth, but PGE2 was elevated during both preterm and term labor. These data suggest that existing levels of PGF2α are sufficient for preterm birth when CAP expression is increased, but term labor requires increases in PGE2, PGF2α, and CAPs. The PGHS-2 messenger RNA expression pattern suggests that it is a CAP.