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The Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom CB2 3EG
Address all correspondence and requests for reprints to: Dr. Dino A. Giussani, The Physiological Laboratory, University of Cambridge, Downing Street, Cambridge, United Kingdom CB2 3EG. E-mail: dag26{at}cam.ac.uk
The present study determined the pituitary-adrenal responses to acute
hypoxemia 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 
145 days), 12 sheep fetuses were instrumented under
halothane anesthesia with an occluder cuff around the umbilical cord,
amniotic and vascular catheters, and a transit-time flow probe around
an umbilical artery. In 6 of the fetuses at 125 days, umbilical blood
flow was reduced by about 30% from baseline for 3 days (UCC), after
which the occluder was deflated. The remaining 6 fetuses acted as
sham-operated controls in which the occluder was not inflated. All
fetuses were then subsequently subjected to 2 periods of acute
hypoxemia, elicited by reducing the maternal inspired fraction of
oxygen (FiO2) at 2 ± 1 and 5 ± 2 days
after the end of cord compression or sham compression. In addition, 4
fetuses from each group were subjected to an ACTH challenge 1–2 days
after the final episode of acute hypoxemia. Maternal and fetal arterial
blood samples were taken at appropriate intervals during cord
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 blood gas status between the groups, basal
plasma cortisol, but not ACTH, concentrations were significantly
greater in compressed fetuses relative to sham controls. However, this
dissociation did not affect a similar increment in fetal plasma ACTH
and cortisol concentrations during acute hypoxemia or in the fetal
plasma cortisol response to the ACTH challenge in either group. An
increase in adrenocortical mass occurred in fetuses preexposed to
partial compression of the umbilical cord relative to sham controls.
The data suggest that fetal exposure to a reversible period of adverse
intrauterine conditions produced by partial compression of the
umbilical cord does not affect the magnitude of the fetal
hypothalamic-pituitary-adrenal axis response to subsequent acute
hypoxemia, but it leads to resetting of basal
hypothalamic-pituitary-adrenal axis function in the fetus. The
mechanism for this resetting may include an increase in adrenocortical
steroidogenic synthetic capacity, but it is not due to a change in
adrenocortical sensitivity to ACTH. Inappropriate fetal glucocorticoid
exposure after reversible periods of adverse intrauterine conditions
has important implications for fetal and postnatal development.
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