Preterm labor is the biggest single cause of neonatal mortality and morbidity. We propose experiments in chronically instrumented pregnant rhesus monkeys in the last third of pregnancy. This chronic whole animal model is the closest available to study mechanisms of labor as they relate to human clinical situations. Different patterns of myometrial activity exist during pregnancy. Through the majority of pregnancy, epochs of myometrial activity lasted several minutes and generate small changes in intrauterine pressure. These epochs, contractures, can be distinguished from the approximately one minute long contractions that occur at labor and delivery and other situations. When labor and delivery occurs, contractures are replaced by contractions. A thorough understanding of the mechanisms that control this switch from contractures to contractions is necessary to determine the causes of term and preterm labor. We hypothesize that changes in the physiology of oxytocin (OT) play important roles in the shift from contractures to contractions that occurs at normal term in our experimental model.
Our Specific Aim i s to investigate the role of oxytocin (OT) in the mechanisms active at term labor and to conduct studies that will determine whether the switch from contractures to contractions represents a true circadian rhythm of intrinsic origin or merely reflects external 24h rhythms. Our proposed studies will utilize both in vivo and in vitro techniques. Parturition is a multifactorial system. To obtain precisely quantifiable and interpretable results we propose five experiments in each of which we will change a single variable at a time in a carefully controlled fashion. We provide preliminary data for four of the five proposed studies. For the first time we have been able to study an instrumented pregnant monkey under constant lighting conditions. We have produced preliminary data to show that maternal body temperature and the switch from contractures to contractions can free run. These studies will provide information on the regulation of different patterns of myometrial activity and suggest procedures for diagnosis and management of preterm labor (e.g. development of efficacious myometrial antagonists) in women.
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