NONHUMAN PRIMATE MODEL OF STRETCH-INDUCED PRETERM LABOR

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Preterm birth remains a significant economic and public health burden and the incidence is rising. Our objective is to develop a nonhuman primate (NHP) model of stretch-induced preterm labor (PTL) to elucidate how mechanical stretch is sensed by the myometrium and fetal membranes. Uterine stretch is often responsible for the onset of PTL in multiple gestation, which accounts for 15% of preterm births and 50% of the increase in preterm birth rates over the last decade. Women with a multiple gestation can be identified by early ultrasound making them an ideal group to target for prophylactic interventions. The unifying hypothesis is that a novel NHP model of uterine stretch will emulate human stretch-induced PTL and define the initiating and subsequent events in the pathogenesis of this type of PTL. Previously, we have defined intracellular mechanisms responsible for stretch-induced expression of labor-associated genes in vitro and now need to establish an animal model in which to test potential therapeutic interventions. We will take advantage of a well-established chronically catheterized NHP model to create stretch-induced PTL by inflating an intra-amniotic balloon. Our NHP model is superior to lower mammalian models of PTL since it shares many features with human pregnancy including placental structure and hormonal control of parturition. This model will allow sequential sampling of myometrium, maternal, and amniotic fluid compartments before and during uterine stretch. If interventions to prevent PTL in multiple gestations are to be achieved, then pathways activated by uterine stretch must be elucidated in a model that emulates the human condition.