PRENATAL MATERNAL STRESS RESCUES CRH-DEFICIENT NEONATAL MICE FROM DEATH.2056

Abstract

The effect of prenatal maternal stress on fetal development and postnatal outcome is unclear. Corticotropin-releasing hormone (CRH)-deficient mice, created by targeted gene disruption, have deficient glucocorticoid (GC) production. CRH-deficient mice uniformly die within the first 12 hr of life with abnormal pulmonary development, but survive with normal pulmonary maturation following prenatal GC treatment of mothers from embryonic day 12(e12) to term (e19). We have asked whether prenatal maternal psychological stress can similarly induce normal pulmonary development and improve postnatal survival in CRH-deficient neonates. CRH-deficient mothers carrying CRH-deficient fetuses received twice daily sessions of restraint stress (30-60 min each) starting e12 or e16 to e19. Following restraint, blood corticosterone levels rose from 1.5 to 15 μg/dL. All mothers were allowed to deliver spontaneously. Among offspring of control mothers not subjected to restraint stress, all (36 offspring from 6 litters) died within the first 12 hr of life from respiratory failure. Among offspring of mothers subjected to restraint stress, 13 of 19 survived at least 48 hr, with 12 surviving up to several weeks until sacrificed for analysis of lung development, which was advanced compared with that of control offspring dying in the perinatal period. This study indicates that prenatal maternal psychological stress, possibly by causing an elevation in GC levels, can improve fetal survival in GC-deficient fetuses. In human pregnancy, pulmonary maturation of premature neonates, which is stimulated by prenatal glucocorticoid treatment, might also be improved following prenatal maternal stress.