Plasma adrenocorticotropin and cortisol concentrations during acute hypoxemia after a reversible period of adverse intrauterine conditions in the ovine fetus during late gestation

The present study determined the pituitary-adrenal responses to acute hypox emia after a period of reversible adverse intrauterine conditions produced by partial compression of the umbilical cord for 3 days in the sheep fetus during late gestation. At 118 +/- 2 days gestation (term is similar to 145 days), 12 sheep fetuses were instrumented under halothane anesthesia with a n occluder cuff around the umbilical cord, amniotic and vascular catheters, and a transit-time flow probe around an umbilical artery. In 6 of the fetu ses at 125 days, umbilical blood now was reduced by about 30% from baseline for 3 days (UCC), after which the occluder was deflated. The remaining 6 f etuses acted as sham-operated controls in which the occluder was not inflat ed. All fetuses were then subsequently subjected to 2 periods of acute hypo xemia, elicited by reducing the maternal inspired fraction of oxygen (FiO(2 )) at 2 +/- 1 and 5 +/- 2 days after the end of cord compression or sham co mpression. In addition, 4 fetuses from each group were subjected to an ACTH challenge 1-2 days after the final episode of acute hypoxemia. Maternal an d fetal arterial blood samples were taken at appropriate intervals during c ord compression, acute hypoxemia, and ACTH challenge for analyses of blood gases, pH, and plasma ACTH and cortisol concentrations. Partial compression of the umbilical cord produced reversible mild fetal asphyxia, a transient increase in fetal plasma ACTH, and a progressive increase in fetal plasma cortisol. At 5 +/- 2 days after the end of compression, despite similar blo od gas status between the groups, basal plasma cortisol, but not ACTH, conc entrations were significantly greater in compressed fetuses relative to sha m controls. However, this dissociation did not affect a similar increment i n fetal plasma ACTH and cortisol concentrations during acute hypoxemia or i n the fetal plasma cortisol response to the ACTH challenge in either group. An increase in adrenocortical mass occurred in fetuses preexposed to parti al compression of the umbilical cord relative to sham controls. The data su ggest that fetal exposure to a reversible period of adverse intrauterine co nditions produced by partial compression of the umbilical cord does not aff ect the magnitude of the fetal hypothalamic-pituitary-adrenal axis response to subsequent acute hypoxemia, but it leads to resetting of basal hypothal amic-pituitary-adrenal axis function in the fetus. The mechanism for this r esetting may include an increase in adrenocortical steroidogenic synthetic capacity, but it is not due to a change in adrenocortical sensitivity to AC TH. Inappropriate fetal glucocorticoid exposure after reversible periods of adverse intrauterine conditions has important implications for fetal and p ostnatal development.