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.
|Zhao, Baohui; Koon, Deanna; Curtis, Allyson L et al. (2007) Identification of 9 uterine genes that are regulated during mouse pregnancy and exhibit abnormal levels in the cyclooxygenase-1 knockout mouse. Reprod Biol Endocrinol 5:28|
|Zhao, Baohui; Koon, Deanna; Bethin, Kathleen E (2006) Identification of transcription factors at the site of implantation in the later stages of murine pregnancy. Reproduction 131:561-71|
|Bethin, Kathleen E; Nagai, Yoshihiko; Sladek, Robert et al. (2003) Microarray analysis of uterine gene expression in mouse and human pregnancy. Mol Endocrinol 17:1454-69|