Fetal endocrine responses to prolonged hypoxemia in sheep

Our aim was to characterize the pattern of release of epinephrine, norepinephrine, arginine vasopressin (AVP), cortisol (hydrocortisone), and prostaglandin E ₂ (PGE ₂) into the fetal circulation during prolonged reductions in uterine blood flow (RUBF). In five sheep RUBF was induced for 24 h, whereas in another five sheep (controls) uterine blood flow was not reduced. Fetal arterial oxygen saturation was decreased from 60.5 ± 3.6 to 20.3 ± 1.6% after 2 h of RUBF and remained significantly reduced for the entire RUBF period. The incidence of fetal breathing movements (FBM) and fetal arterial pH were reduced from 36.7 ± 4.5 min/h and 7.36 ± 0.01 to 4.3 ± 1.8 min/h and 7.13 ± 0.02, respectively, after 2 h of RUBF, but both had returned to control levels after 14 h. Fetal plasma AVP and epinephrine concentrations were increased from 4.4 ± 0.5 pg/ml and 0.19 ± 0.05 ng/ml to 333.8 ± 41.5 pg/ml and 1.5 ± 0.6 ng/ml, respectively, after 2 h and then declined to near control levels after 12 h of RUBF. Fetal plasma norepinephrine and cortisol concentrations were increased from 1.3 ± 0.4 and 4.0 ± 2.2 ng/ml to 6.1 ± 1.8 and 13.5 ± 4.1 ng/ml, respectively, after 2 h of RUBF, and both remained significantly elevated throughout the remainder of the RUBF period. Fetal plasma PGE ₂ concentrations progressively increased (from 1.9 ± 0.4 to 8.8 ± 1.7 nmol/l at 12 h) as the duration of RUBF increased and were still significantly elevated after 24 h. The time course for the increase in PGE ₂ during RUBF was very similar to the increases in arterial pH and in the incidence of FBM. We conclude that the endocrine responses of the fetus to RUBF change with time and that many of the acute responses are not sustained. Furthermore, the gradual return in the incidence of FBM does not result from a decline in elevated plasma concentrations of PGE ₂.