GENETIC ANALYSIS OF MYOMETRIAL FUNCTION IN PARTURITION

Washington University, Saint Louis MO

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Linked publications & trials

Abstract

DESCRIPTION (Adapted from applicant's description): Despite advances in modem medicine, preterm labor continues to complicate 7-10% of all pregnancies. Infants delivered prematurely account for 85% of all perinatal mortality and morbidity. Clearly, an intervention designed to delay or prevent premature labor would be of great benefit. In order to study factors that effect parturition, we will develop a system that allows manipulation of uterine myometrial genes in the mouse. Using the reverse tetracycline trans-activator system, specific genes can be selectively expressed in the presence of doxycycline at chosen times during pregnancy. To begin to utilize this system to explore the roles of cAMP and oxytocin receptor in myometrial quiescence and contractility, respectively, this proposal seeks to fuse the tetracycline transactivator to smooth muscle promoters. The role of cAMP in relaxation in non-uterine smooth muscle has been well-documented. Furthermore, beta- adrenergic agonists, which act by increasing cAMP levels, are widely used as tocolytic agents. The reverse tetracycline trans-activator system fused with a smooth muscle specific promoter will be used to over-express phosphodiesterase in uterine myometrium and study the effects of decreased myometrial cAMP on parturition in a mouse model. The results of these studies will help elucidate the parturition cascade in both term and preterm labor. In the future, this system will be used to study factors involved in stimulation of myometrial contraction rather than maintenance of uterine quiescence.