Our three interrelated hypotheses are 1) myometrial activity throughout pregnancy plays an important role in the maturation of the fetal central nervous system (CNS) by providing a continuous stream of afferent stimulation to the fetal CNS, 2) myometrial activity plays an important role in the maturation of the fetal hypothalamo-hypophyseal-adrenal axis (HHAA), 3) fetal adrenal cortisol plays a role in fetal CNS maturation as immaturation of other vital fetal organ system, e.g. lung.
Specific Aim 1 will determine the mechanisms whereby myometrial contractile activity alters normal late gestation activity in, and maturation of, fetal sheep, a) ECOG; b) EOG; c) breathing; d) skeletal muscular movement; e) swallowing movements; and f) behavioral patterns. We will study normal maturation and determine alterations in maturation in situations in which the effects of spontaneous contractures are modified, i.e., experimentally produced polyhydramnios (PH) and oligohydramnios (OH). We will also study effects of oxytocin (OT) induced contractures and modification by PH and OH of effects on the fetus of OT induced contractures.
Specific Aim 2 will determine changes in the fetal HHAA that accompany experimental paradigms in which we alter contracture activity and situations in which effects of spontaneous and OT induced contractures on the fetus are modified. The results will be obtained in the same animals as Specific Aim 1, thus strengthening extrapolations and correlations of biophysical and endocrine data.
Specific Aim 3 will determine effects of the fetal HHAA on maturation of Specific Aim 1 variables. We will observe maturation in a) fetuses infused with cortisol to bring forward the normal preterm fetal plasma cortisol rise and b) sham-adrenalectomized and c) adrenalectomized fetuses. We have assembled the necessary biophysical and endocrine methodologies to observe these neural and endocrine features and integrate continuous data over many days from significant features whose interrelated actions and consequences can only be studied in the whole animal. Clinical situations such as OH have marked effects on fetal development. Various investigators have shown that alteration in the intrauterine environment can modify fetal CNS and endocrine maturation. Our studies will utilize the most commonly used fetal experimental animal to assess the role of myometrial activity and altered amniotic fluid volume on fetal development.
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