Tissue DNA Synthesis in the Preterm Ovine Fetus Following 8 Hours of Sustained Hypoxemia

Abstract

Objective: Protein synthesis is significantly decreased in the near-term ovine fetus in response to induced hypoxemia of several hours' duration. We therefore sought to determine the extent to which DNA synthesis rates as an index of tissue mitotic activity are also affected by similarly induced compromises in fetal oxygenation.

Methods: Fetal sheep were studied at 0.75 of gestation during a normoxic control period and an 8-hour experimental period of either sustained hypoxemia induced by lowering maternal inspired oxygen concentration of 11-8% (hypoxia group, n = 7) or continued exposure to room air (control group, n = 5). To estimate DNA synthesis rate, [³H]-thymidine (1 mCi/kg) was injected intravenously into each fetus at the beginning of the experimental period.

Results: Sustained hypoxemia with a reduction in fetal arterial O₂ content from (mean ± standard error of the mean) 4.3 ± 0.1 to 1.5 ± mmol/L by the end of study resulted in a variable degree of fetal acidemia, 7.26 ± 0.03 (range from 7.41 to 7.10), which was entirely metabolic in nature.

Conclusion: The DNA synthesis rates of most tissues were not significantly changed by the 8 hours of sustained hypoxemia, suggesting that restrictions in protein synthesis in response to fetal hypoxia are initially due to a differential effect on nonmitotic synthetic processes at this stage of development. However, selective decreases in the DNA synthesis rates of the hippocampus (approximately 50%, P < .01), adrenals (approximately 48%, P < .05), and left and right myocardial ventricles (approximately 42% and 27%, respectively, P = .08) were evident which may reflect altered mitotic activity in response to tissue related changes in energy expenditure.