The three integrated projects test fundamental hypotheses related to fetal neuro-endocrinology, parturition and regulation of the myometrium in parallel experiments in chronically instrumented pregnant sheep and pregnant rhesus monkey preparations. The Reproductive Studies Research Group at Cornell has developed the animal techniques, computerized biophysical systems and biochemical and endocrinological methods required to study these two experimental models. We propose a multidisciplinary approach in which selected single variables will be changed with appropriate statistical analysis. Project 1 continues seven years of NIH funded work to study initiation and completion of parturition in sheep. It tests the hypothesis that both fetal and maternal neural and hormonal mechanisms regulate epochs of chronic long-lasting myometrial activity and contractures, throughout gestation and that one or more of these factors regulate the change of contractures to labor and delivery contractions. It examines regulation of contractures and contractions by arachidonic acid metabolites, steroids, uterine stretch and starvation. Projects 1 and 2 examine the fetal hypothalamo-hypophyseal- adrenal axis (HHAA) using immunocytochemical techniques and stereotaxic lesions of the fetal hypothalamus. They focus on histological development of oCRF containing neurons and the fetal PVN's role in pulsatile secretion of fetal ACTH. They will evaluate effects of fetal PVN lesions on glucocorticoid feedback and secretion of ACTH in response to stress stimuli, and will determine if PVN oCRF-containing neurons are involved in the increased activity of the fetal HHAA which may play a central role in initiation of parturition. Project 3 examines similar systems in the rhesus monkey. We will develop the capability to lesion the PVN and place lateral ventricular catheters in fetal rhesus monkeys at 120 days gestation to study the role of CRF and AVP in regulation of the fetal rhesus HHAA. Control of the primate myometrium will be investigated both in vitro and in vivo. We will undertake immunocytochemistry of the fetal hypothalamus. Prematurity and complications of delivery are major obstetric problems and increase perinatal mortality and morbidity. These experiments will define similarities and differences between sheep and non-human primates.
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