Poster session I Clinical obstetrics, epidemiology, fetus, medical-surgical complications, neonatalogy, physiology/endocrinology, prematurity: Abstracts 87 - 236| Volume 208, ISSUE 1, SUPPLEMENT , S106, January 01, 2013

231: Prenatal hypoxia programs increased hepatic mitochondrial gene expression in guinea pig (GP) offspring


      Intrauterine hypoxia is a prenatal insult that contributes to fetal organ dysfunction. Permanent changes in organ function of the offspring may be mediated via programming mechanisms. We previously reported that chronic fetal hypoxia increases mitochondrial enzyme activity associated with fatty acid oxidation (FAO; MCAD, medium chain acyl dehydrogenase) and oxidative phosphorylation (OXPHOS; CCO, cytochrome c oxidase) in 90d old GP livers compared to their normoxic controls (SGI2012 Abstract #F120). We hypothesize that increased mitochondrial enzyme activity by intrauterine hypoxia is mediated via upregulation of target genes [Hepatic MCAD (protein & mRNA), PPAR α & γ (mRNA, peroxisome proliferator-activated receptors)] associated with mitochondrial protein expression.

      Study Design

      Pregnant GPs were exposed to either room air (normoxia NMX) or 10.5% O2 (hypoxia HPX) for 14d prior to term (65d). Fetal GPs were allowed to deliver and male offspring were selected for study and housed in room air. At 90d, offspring (N=11-12/grp) were anesthetized, body and liver weights measured, and right liver lobes excised and frozen (−80oC). MCAD protein of isolated mitochondrial fractions were measured by Western analysis and normalized to Porin. MCAD & PPARα & γ mRNA levels were measured by RTPCR using appropriate primers, normalized to 18srRNA.


      Chronic hypoxia had no effect on body or liver weights. Exposure to prenatal hypoxia increased (p<.05) both MCAD protein (NMX vs HPX 0.35±0.10 vs 0.83±0.17) & mRNA (NMX vs HPX 0.57±0.05 vs 0.81±0.05) levels of offspring livers. PPARα (NMX vs HPX 0.14±0.02 vs 0.25±0.03) but not PPARγ mRNA (NMX vs HPX 0.21±0.04 vs 0.28±0.05) levels were increased (p<.05) by prenatal hypoxia in offspring livers.


      These results suggest that in-utero exposure to chronic hypoxia upregulates hepatic MCAD enzymatic activity via transcription factors that regulate FAO, suggesting that prenatal hypoxia programs altered liver metabolism in the offspring (NIH HL49999).