Sheila Lorente-Pozo1, Anna Parra-Llorca2, Antonio Núñez-Ramiro2, María Cernada2, David Hervás3, Nuria Boronat4, Juan Sandoval5, Maximo Vento2. 1. Neonatal Research Group, Health Research Institute La Fe, Valencia, Spain. 2. Neonatal Research Group, Health Research Institute La Fe, Valencia, Spain; Division of Neonatology, University and Polytechnic Hospital La Fe, Valencia, Spain. 3. Department of Biostatistics, Health Research Institute La Fe, Valencia, Spain. 4. Division of Neonatology, University and Polytechnic Hospital La Fe, Valencia, Spain. 5. Biomarkers and Precision Medicine Unit, Health Research Institute La Fe, Valencia, Spain.
Abstract
OBJECTIVES: To determine whether the amount of oxygen provided during postnatal stabilization changes the DNA methylome in preterm infants. STUDY DESIGN: This prospective, observational study included 32 preterm infants ≤32 weeks of gestation who received oxygen in the delivery room. Patients were monitored using a respiratory function monitor to determine the amount of oxygen received upon stabilization. Blood samples were processed for comparison of DNA methylation before and after resuscitation using a DNA methylation high-resolution microarray Infinium Human DNA methylation EPIC 850K BeadChip. RESULTS: The median amount oxygen provided to preterm infants during stabilization was 644 mLO2/kg. Male sex and vaginal delivery were associated with increased oxygen needs. There were 2626 differentially methylated CpGs representing 1567 genes that showed an association with oxygen load selected and, of these, 85% were hypomethylated. We found that oxygen loads of >500 mLO2/kg changed the methylation pattern of the selected CpGs. Genes associated with these CpGs were "enriched" in KEGG pathways involved in cell cycle progression, DNA repair, and oxidative stress. CONCLUSIONS: The oxygen load provided upon resuscitation modified the DNA methylome. Differential methylation may lead to altered expression of genes related to cell cycle progression, oxidative stress, and DNA repair. The reversibility of these early epigenetic changes is unknown but merits further study.
OBJECTIVES: To determine whether the amount of oxygen provided during postnatal stabilization changes the DNA methylome in preterm infants. STUDY DESIGN: This prospective, observational study included 32 preterm infants ≤32 weeks of gestation who received oxygen in the delivery room. Patients were monitored using a respiratory function monitor to determine the amount of oxygen received upon stabilization. Blood samples were processed for comparison of DNA methylation before and after resuscitation using a DNA methylation high-resolution microarray Infinium Human DNA methylation EPIC 850K BeadChip. RESULTS: The median amount oxygen provided to preterm infants during stabilization was 644 mLO2/kg. Male sex and vaginal delivery were associated with increased oxygen needs. There were 2626 differentially methylated CpGs representing 1567 genes that showed an association with oxygen load selected and, of these, 85% were hypomethylated. We found that oxygen loads of >500 mLO2/kg changed the methylation pattern of the selected CpGs. Genes associated with these CpGs were "enriched" in KEGG pathways involved in cell cycle progression, DNA repair, and oxidative stress. CONCLUSIONS: The oxygen load provided upon resuscitation modified the DNA methylome. Differential methylation may lead to altered expression of genes related to cell cycle progression, oxidative stress, and DNA repair. The reversibility of these early epigenetic changes is unknown but merits further study.
Authors: C Iranzo-Tatay; D Hervas-Marin; J Sandoval; L Rojo-Moreno; L M Rojo-Bofill; D Garcia; F J Vaz-Leal; I Calabria; L Beato-Fernandez; S Oltra Journal: Transl Psychiatry Date: 2022-01-10 Impact factor: 7.989