Myometrial Gq signaling in the progression of labor

Washington University, Saint Louis MO

Investigators

Linked publications & trials

Abstract

The mechanisms controlling the timing and progression of labor remain incompletely understood. Through studies on knockout mice it has been demonstrated that prostaglandin and oxytocin pathways are important contributors to the progression of labor. Cox-l-deficient mice do not undergo luteolysis at term and manifest delayed parturition. Cox-l- deficient mice have low prostaglandin F2 alpha levels and fail to induce the oxytocin receptor. Mice deficient in both oxytocin and Cox-1 undergo luteolysis and induce the oxytocin receptor. However, levels of both oxytocin and prostaglandin F2 alpha remain low and these mice exhibit protracted and dysfunctional labor. Considering that both the oxytocin receptor and the prostaglandin F2 alpha receptor are Gq coupled-protein receptors it is probable that signaling from these receptors is important in the initiation and progression of labor. Our goal is to generate transgenic mice with tetracycline-inducible expression of a dominant-negative Gq alpha peptide in order to delineate the pathways regulating the timing and progression of labor. We will assess the effect on parturition arising from the inhibition of Gq protein-coupled receptor signaling thereby further elucidating the signaling pathways controlling the timing and progression of labor.