We will test the hypothesis that both fetal and maternal neural and hormonal mechanisms regulate epochs of tonic long lasting myometrial activty, contractures, throughout gestation and that one or more of these factors regulate the change of myometrial contractures to labor and the delivery contractions. We will investigate the regulation of contractures by arachidonic acid metabolites (AAM) and the role of steroids, stretch and starvation. We will use chronically catheterized fetal sheep and change selected single variables in controlled experiments. This experimental model permits longterm sequential studies of myometrial activity without complication by tocolytic agents or excessive restraint. We have designed data acquisition systems to quantify myometrial EMG activity for rapid, precise, and clear quantitative measurement of different types of myometrial activity. We have added stereotaxic neurosurgical techniques and histochemical methods to our procedures. We will investigate: I. AVP's role in control of ACTH release folowing short term stresses and during increased fetal hypothalamo-hypophyseal adrenal activity that results in initiation of parturition in sheep. II. distribution of AVP in fetal hypothalamus and placenta. III. regulation of myometrial activity by peripheral factors specifically AAM. IV. the control of the myometrium in the non-pregnant sheep. Knowledge of causation and treatment of premature labor and myometrial mechanisms investigated will improve understanding of the mechanisms whereby factors such as maternal stress, alcohol, caffeine and nicotine affect myometrial function. Preterm labor and abnormal labor patterns are important causes of perinatal mortality and morbidity.
