Sexually dimorphic methylation patterns characterize the placenta and blood from extremely preterm newborns

Sexually dimorphic methylation patterns characterize the placenta and blood from extremely preterm newborns

Health outcomes among children born prematurely are known to be sexually dimorphic, with male infants often more affected, yet the mechanism behind this observation is not clear. CpG methylation levels in the placenta and blood also differ by sex and are associated with adverse health outcomes. We c...

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Bibliographic Details
Published in:BMC biology Vol. 21; no. 1; pp. 1 - 12
Main Authors: Santos, Hudson P, Enggasser, Adam E, Clark, Jeliyah, Roell, Kyle, Zhabotynsky, Vasyl, Gower, William Adam, Yanni, Diana, Yang, Nou Gao, Washburn, Lisa, Gogcu, Semsa, Marsit, Carmen J, Kuban, Karl, O'Shea, T. Michael, Fry, Rebecca C
Format: Journal Article
Language:English
Published: London BioMed Central Ltd 23-08-2023
BioMed Central
BMC
Subjects:
Analysis
Attention deficit hyperactivity disorder
Autism
Blood
Body mass index
Care and treatment
Cell culture
Child health
Chromosomes
CpG islands
Differentiation
Diseases
DNA methylation
Enrichment
Epigenetic inheritance
Epigenetics
Females
Fetuses
Gender differences
Genes
Gestational age
Health aspects
Heterogeneity
Infants
Infants (Newborn)
Infants (Premature)
Males
Methylation
Molecular mechanics
Neonates
Placenta
Preterm birth
Proteins
Sexual dimorphism
United States
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Summary:Health outcomes among children born prematurely are known to be sexually dimorphic, with male infants often more affected, yet the mechanism behind this observation is not clear. CpG methylation levels in the placenta and blood also differ by sex and are associated with adverse health outcomes. We contrasted CpG methylation levels in the placenta and neonatal blood (n = 358) from the Extremely Low Gestational Age Newborn (ELGAN) cohort based on the EPIC array, which assays over 850,000 CpG sites across the epigenome. Sex-specific epigenome-wide association analyses were conducted for the placenta and neonatal blood samples independently, and the results were compared to determine tissue-specific differences between the methylation patterns in males and females. All models were adjusted for cell type heterogeneity. Enrichment pathway analysis was performed to identify the biological functions of genes related to the sexually dimorphic CpG sites. Approximately 11,500 CpG sites were differentially methylated in relation to sex. Of these, 5949 were placenta-specific and 5361 were blood-specific, with only 233 CpG sites overlapping in both tissues. For placenta-specific CpG sites, 90% were hypermethylated in males. For blood-specific CpG sites, 95% were hypermethylated in females. In the placenta, keratinocyte differentiation biological pathways were enriched among the differentially methylated genes. No enrichment pathways were observed for blood. Distinct methylation patterns were observed between male and female children born extremely premature, and keratinocyte differentiation pathways were enriched in the placenta. These findings provide new insights into the epigenetic mechanisms underlying sexually dimorphic health outcomes among extremely premature infants.
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ISSN:1741-7007
1741-7007
DOI:10.1186/s12915-023-01662-7