Fetal and maternal endocrine responses to reduced uteroplacental blood flow

In clinical practice, falling or reduced maternal estrogen levels are commonly regarded as indicators of fetal distress. However, experimental studies in primate animal models demonstrate that changes in maternal estradiol concentrations vary in response to reduced uteroplacental blood flow and are elevated during fetal hypoxemic stress, suggesting an increase in fetal adrenal precursor steroids. We studied the effects of graded reductions in maternal distal aortic blood flow (Q_da) on the fetal MCR of dehydroepiandrosterone (D; MCR-D), the fetal production rate of D (PR-D), and changes in maternal and fetal plasma concentrations of D, D sulfate, cortisol, androstenedione, estrone (E₁), and estradiol (E₂) and in fetal plasma ACTH, PRL, and LH. A continuous iv infusion of [7-³H]D was administered to fetuses in five pregnant baboons (Papio anubis) at 155-165 days gestation (term, 184 days) for 270 min. A 50% reduction in mean distal aortic blood flow was imposed after 60 min by means of partial occlusion of the aorta with a snare device, which was released at 180 min. Maternal and fetal blood samples were collected at 10-min intervals from 30-60, 120-180, and 240-270 min. Equilibrium concentrations of [³H]D in fetal plasma were determined, and the MCR-D and PR-D were calculated for each of the three levels of Q_da, corresponding to the control, occlusion, and release intervals. Concentrations of steroid and peptide hormones in maternal and fetal plasma were determined by RIA, and arterial blood pH, pO₂, and pCO₂ were measured. Control fetal PR-D (mean ± SE, 4.4 ± 2.0 mg/day) rose significantly during aortic occlusion accompanied by fetal hypoxemia (11.8 ± 3.1 mg/day; P < 0.05) and remained elevated with release of the aortic constriction (13.8 ± 2.9 mg/day). Changes in fetal MCR-D were variable and not statistically significant. Among the maternal plasma steroids, only E₁ and E₂ increased significantly, doubling from control values during aortic occlusion and increasing by another 50% after release (P < 0.05). There was a significant correlation between fetal PR-D and maternal plasma E₂ and E₁ concentrations (r² = 0.76 and 0.71, respectively; P < 0.01). Fetal hypoxemia was associated with dramatic increases in fetal plasma D, D sulfate, androstenedione, E₁, and E₂. No significant change occurred in fetal plasma cortisol, which tended to decline throughout the study. We observed a dramatic and sustained increase in fetal plasma ACTH during the period of reduced Q_da and for 90 min thereafter, but no change in PRL or LH. We conclude that placental hypoperfusion with fetal hypoxemic stress results in elevated maternal and fetal E₁ and E₂ levels, which represent increased production of fetal androgen. Fetal adrenal activation during hypoxemic stress is probably mediated by ACTH, but not by PRL or LH.