Cord blood genomic analysis highlights the role of redox balance.
Neonates are exposed to elevated levels of reactive oxygen species as they transition from a hypoxic intrauterine to a normoxic extrauterine environment at birth. This increased oxidative stress is associated with neonatal morbidity. Current antioxidant supplementation treatment strategies have yet to translate into improved neonatal outcomes. Our understanding of a newborn's intricate redox balance, particularly at the genomic level, remains limited. Here, we performed genomic microarray analyses (approximately 14,500 genes) on extracted mRNA from umbilical cord whole blood at term gestation (n=10). Bioinformatic analyses identified 282 genes (2.0%) that were consistently present within the highest quintile of expressed genes. These genes were highly associated with oxidant stress and included superoxide dismutase 1, catalase, peroxiredoxins, and uncoupling proteins. Pathway analyses identified statistically significantly overrepresented functional pathways including "oxidative stress," "oxidative stress response mediated by nuclear factor-erythroid 2-related factor," "hypoxia-inducible factor signaling," and "mitochondrial dysfunction" (p<0.05). These results suggest that neonates require high levels of antioxidants and an intricate cellular redox balance to ensure a successful transition to the extrauterine environment. Understanding the genes necessary to maintain this delicate redox balance may lead to the development of alternative treatment strategies.
Maron
Jill L
JL
Division of Newborn Medicine, Department of Pediatrics, Floating Hospital for Children at Tufts Medical Center, Boston, MA 02111, USA. jmaron@tuftsmedicalcenter.org
Johnson
Kirby L
KL
Parkin
Christopher
C
Iyer
Lakshamanan
L
Davis
Jonathan M
JM
Bianchi
Diana W
DW
D002374:Catalase / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism*; D016678:Genome; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D046228:Microarray Analysis; D050983:NF-E2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
D050983:NF-E2 Transcription Factor; C000606290:SOD1 protein, human; D054464:Peroxiredoxins; D002374:Catalase; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1