The objectives of this Program Project are to define the nature of the metabolic events of the fetus, amniotic fluid, fetal membranes, and uterine decidua that constitute a metabolic communication system. The observations of other investigators as well as the results of studies in this laboratory suggest that maturation of the fetus is associated with the initiation of metabolic signals that eventuate in parturition. The terminal events in labor appear likely to be the release by the fetal membranes and/or decidua of lysosomal phospholipase A2 which catalyzes the release of non-esterified arachidonic acid from its chorion leave phospholipid storage form. The residue of the phospholipid from phospholipase A2 action is lysolecithin, a potent cytolytic agent(s) that will bring about further cell disruption and the autocatalytic process is underway. The release of arachidonic acid from storage phospholipid is requisite to prostaglandin synthesis in the decidua. The initiation of these events appears likely to occur as the consequence of fetal direction which has its origin in fetal brain maturation through pituitary-fetal adrenal secretory processes. Preparatory metabolic events in the ultimate initiation of parturition appear also to reside in fetal signals. Central amongst these is an increase in activity of phosphatidic acid phosphohydrolase in both the fetal lungs and the fetal membranes. The increase in this enzyme is likely responsible for augmented phosphatidylcholine synthesis in lung, resulting in surfactant elaboration, and for the accumulation of phospholipid rich in arachidonic acid in the fetal membranes. The hypothesis upon which this project is based envisions, therefore, that the fetus, through maturation, normally controls its own destiny. BIBLIOGRAPHIC REFERENCES: Schwarz, B. E., F. M. Schultz, P. C. MacDonald, and J. M. Johnston. Initiation of Human Parturition: IV. Demonstration of Phospholipase A2 in the lysosomes of Human Fetal Membranes. Am. J. Obstet. Gynecol. 125:1089-1092, 1976. Milewich. L., N. F. Gant, B. E. Schwarz, G. Chen, and P. C. MacDonald. Initiation of Human Parturition: VIII. Metabolism of Progesterone by Fetal Membranes of Early and Late Human Gestation. Obstet. Gynecol., In press, March 1977.
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NIH ExPorter