Researchers have uncovered different methylation patterns among male and female infants born very prematurely, which could account for the differences in health outcomes they face. A University of North Carolina at Chapel Hill-led team examined CpG methylation levels within placenta and neonatal blood samples from 358 infants from the Extremely Low Gestational Age cohort — infants in the cohort had a mean gestational age of 26 weeks. As they report in BMC Biology, the researchers assayed more than 850,000 CpG sites and conducted sex-specific epigenome-wide association analyses. They found about 11,500 differentially methylated sites between the male and female infants, nearly 6,000 of which were placenta-specific and about 5,300 of which were blood specific. Generally, placenta samples from male infants were hypermethylated, while blood samples exhibited hypomethylation. Blood samples from female infants, meanwhile, were largely hypermethylated. These methylation differences affected genes including NAB1, HMGCS1, and CALM1 in the placenta and LOC644649 and RBMS1 in blood. A further Gene Ontology analysis found keratinocyte differentiation to be significantly associated with the placenta-specific CpG loci. "These findings provide new insights into the epigenetic mechanisms underlying sexually dimorphic health outcomes among extremely premature infants," the researchers write.