Compelling data from several species demonstrates that glucocorticoid treatments both antenatally and in early postnatal life have beneficial effects on lung development and surfactant production. However, they also cause growth retardation of organ systems and the placenta. In addition, such treatments are known to produce long term deficits in the function of various physiological systems (e.g., blood pressure, glucose metabolism) that are similar in many respects to changes seen with aging in normal individuals. However, these changes occur much earlier in life and follow inappropriate glucocorticoid exposure at during development. Human demographic data indicate that the majority of working women who become pregnant will work for a large proportion of their pregnancy. Central to the present proposal is the thesis that working during pregnancy represents a psychological stress to the mother that may increase as pregnancy progresses. While data from human and animal studies has accumulated on immediate perinatal outcomes of stress during pregnancy, little data exists on the long term consequences of such stress on the health or life span of progeny in later life. This application proposes to use pregnant rats subjected to psychological stress throughout pregnancy to study aging of offspring. The hypothesis is: Female rats subjected to daily stress through pregnancy produce offspring that age and die more quickly than progeny from non stress controls. The paradigm used places pregnant mothers in a standard rat restraint chamber for 45 min per day throughout pregnancy starting on the day of breeding. The endpoints examined are the baroreflex, glucose tolerance and aged at death. The rat is a well established model for studies in aging and the prenatal maternal psychological stress used in this model is known to cause long term deficits in the hippocampus (a critical aging-related brain area) of progeny. If funded, further development of this model will: 1) provide sorely needed information on long term consequences of psychological stress during pregnancy, 2) ultimately provide information on windows of risk for premature aging and 3) help in the design of strategies to minimize and/or prevent the occurrence of such undesirable consequences.
