Fetal and maternal endocrine responses to reduced uteroplacental blood flow.

Abstract

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 (Qda) 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 i.v. 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 Qda 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 less than 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 less than 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 less than 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 Qda and for 90 min thereafter, but no change in PRL or LH.(ABSTRACT TRUNCATED AT 400 WORDS)

Fetal Programming: Prenatal Testosterone Excess Leads to Fetal Growth Retardation and Postnatal Catch-Up Growth in Sheep

“…Alternatively, the growth retardation observed in the stress models may be facilitated via increased sex steroid levels. In subhuman primates, increases in plasma androgen and estrogen metabolites were noted after the induction of hypoxic conditions through arterial ligation, suggesting that fetal and maternal stress have the potential to cause significant increases in sex steroid levels (44). In these studies it is also unclear whether the effects of prenatal T treatment, if any, are due to its androgenic action or are the result of its aromatization to estradiol.…”

Fetal adrenal and middle cerebral artery Doppler velocimetry in high‐risk pregnancy

“…Compared to total fetal body weight, they are 20-fold heavier than in the adult 16 . The fetal adrenals respond to stress, such as hypoxemia, by producing more dihydroandrostenedione (DHA), DHA sulfate, and their metabolites 17 . In animal studies, a three-fold increase in adrenal blood flow has been demonstrated during hypoxia 3 .…”

Developmental programming of cardiovascular disorders: Focus on hypertension

“…Adrenal weights of prenatal testosterone-treated female fetuses were clearly larger than controls [25], suggestive of adrenal involvement. Conversely, increases in plasma androgen and estrogen metabolites were noted in subhuman primates following induction of hypoxic conditions through arterial ligation, suggesting that fetal and maternal stress have the potential to cause significant increases in sex steroids [30]. Recent studies have found a positive correlation between fetal plasma testosterone and cortisol in humans [31].…”