Chronic Hypoxia and Developmental Regulation of Cytochrome C Expression in Rats

OBJECTIVE To test the hypothesis that chronic hypoxia upregulates cytochrome c expression in heart, brain, and liver of fetal and maternal rats. METHODS Time-dated pregnant Sprague-Dawley rats were divided into normoxic and hypoxic (48 hours of 10.5% oxygen from days 19 to 21) groups, and were killed on day 21. Tissue levels of cytochrome c in heart, brain, and liver were determined by using monoclonal antiserum for cytochrome c. RESULTS Chronic hypoxia caused a decrease in fetal body weight (5.3 +/- 0.1 to 4.7 +/- 0.1 g) and an increase in heart/body weight ratio (0.0048 +/- 0.0001 to 0.0061 +/- 0.0002). Cytochrome c levels were 4-, 2.6-, and 13-fold higher in heart, liver, and brain, respectively, of the mother than of the fetus. Chronic hypoxia did not change cytochrome c levels in maternal tissues but caused a 70% increase and 54% decrease in cytochrome c levels in the fetal heart and liver, respectively. No difference was observed in the fetal brain. CONCLUSIONS The results suggest that expression of cytochrome c is tissue specific and developmentally regulated. Chronic hypoxia showed differential regulation of cytochrome c levels both developmentally and tissue specifically. The increased sensitivity of cytochrome c in fetal tissue to chronic hypoxia is likely to represent a fetal adaptive mechanism to the stress of chronic hypoxia.