Chronic intrauterine hypoxia inhibits Cytochrome c Oxidase (CCO) activity in maternal and fetal guinea pig liver

Chronic intrauterine hypoxia is a leading cause of fetal morbidity and mortality. Decreases in fetal liver perfusion and O2 availability, can contribute to liver damage associated with metabolic dysfunction. We hypothesize that chronic hypoxia reduces mitochondrial function by inhibiting the activity of enzymes in the electron transport chain (ETC). Methods Pregnant guinea pigs were housed in a normoxic or a hypoxic (10.5% O2) chamber for 14 days prior to term (65 days). At term, the pregnant sows were anesthetized and fetuses delivered via hysterotomy. The maternal and fetal right liver lobes were harvested and snap frozen in liquid N2 and stored at −80 C. Liver mitochondria (mito) were isolated and Cytochrome c Oxidase (CCO) specific activity (nmol/min/ug of mito protein) was measured as an index of mito function. Results Hypoxia significantly reduced CCO activity in both maternal and fetal liver. Maternal CCO activity was reduced by 55% from −1.19 +/− 0.12 to −0.53 +/− 0.11 (n=3, p<.05), and fetal CCO activity decreased by 31% from −0.16 +/− 0.19 to −0.109 +/− 0.009 (n=4, p<.05). Conclusions Chronic hypoxia reduces the capacity of liver CCO to oxidize cytochrome c. This suggests that mito function in hypoxic fetal liver is compromised which may have implications in metabolic programming of affected offspring. Supported by NIH HL49999 (LT) and HL072751 (YA)