Preterm Baboons Research Articles

Effect of maternal administration of the antiestrogen ethamoxy triphetol throughout the last third of baboon gestation upon neonatal corticoid production

The present study determined in baboon neonates whether corticoid production, which is markedly different in preterm baboon neonates, newborns and adult baboons is regulated by estrogen, and therefore, altered by maternal administration of the antiestrogen ethamoxytriphetol (MER-25) throughout the final third of baboon gestation. The metabolic clearance rate (MCR), transfer constant (ρ), production (PR) and secretion (SR) rates of cortisol (F) and cortisone (E) were determined by continuous infusion of [3H] F and[14C]E in baboon neonates delivered spontaneously to untreated mothers and to mothers, which had received MER-25 p.o. (15 mg/kg BW) daily throughout the final third of baboon gestation.MCR-E exceeded (P < 0.05) MCR-F in both groups. The ρ F→E was greater than ρ E→F in neonates of untreated (3.5 fold, P < 0.005) and MER-25-treated (1.8 fold, P < 0.025) mothers. Mean (±SE) ρ F→E was lower (P < 0.01) in neonates delivered to mothers, which had received antiestrogen (29.2±4.4%) than in untreated mothers (59.7±8.9%). Mean (±SE) conversion ratio of F→E (F→E — E→F) was lower (P < 0.05) in neonates of antiestrogen-treated (13.7±5.5) than of untreated (41.9±10.9) mothers. Since ρ is the proportion of blood PR of precursor converted to product (i.e. F to E) it is evident that neonatal F and E production in baboons are influenced by maternal administration of antiestrogen. Thus, mean (±SE) PR-E was greater (P < 0.05) than PR-F in controls (6.79±1.23 (E), 3.69± 0.55 (F) μg/min/kg BW), but not in neonates of antiestrogen-treated mothers (4.51±1.12 (E), 3.56±0.98 (F) μg/min/kg BW).Assuming that MER-25 interfered with the action of estrogen in the fetus, our results suggest that estrogen, which is produced in increasing amounts into the maternal and fetal circulation with advancing baboon gestation, regulates the pattern of baboon fetal corticosteroidogenesis, a pattern which is distinct from that in newborns and adults and presumably represents maturational events leading to extrauterine self sufficiency.

Perinatal Circulation

Investigation in bronchopulmonary dysplasia (BPD) has been seriously hampered by the lack of a suitable animal model. The consistent development of BPD in preterm baboons (Papio cynocephalus) with hyaline membrane disease (HMD) who were treated with 95–100% inspired oxygen and supported with mechanical ventilation for more than 1 week is reported. One term (173 days) and nine preterm (134–147 days) pregnancies were delivered by cesarean section with birth weights 495–988 g. Amniotic fluid lecithin: sphingomyelin (L/S) ratios ranged from 0.47 to 1.00. The six animals with L/S ratios ⩽ 0.62 developed HMD. The clinical and radiologic course was indistinguishable from HMD in preterm humans. HMD was confirmed pathologically in two animals dying acutely. One of the remaining four was supported with supplemental oxygen as needed and remains a long-term survivor of HMD. The other three were maintained in 95–100% oxygen. A clinical and radiographic picture similar to that of human BPD developed in each and was pathologically confirmed. The preterm baboon appears to be a suitable animal model for investigation of the etiology, pathophysiology, prevention, therapy, and long-term sequelae of HMD and BPD.