Comparison of genome-wide and gene-specific DNA methylation between ART and naturally conceived pregnancies

Nir Melamed, Sanaa Choufani, Louise E. Wilkins-Haug, Gideon Koren, Rosanna Weksberg

פרסום מחקרי: פרסום בכתב עתמאמרביקורת עמיתים

76 ציטוטים ‏(Scopus)

תקציר

Data linking assisted reproductive technologies (ART) with aberrant DNA methylation is limited and inconclusive. In addition, most studies to date have analyzed only a small number of CpG sites and focused on methylation changes in placentas, while data on cord blood are scarce. Our aim was to compare DNA methylation in cord blood samples from ART (N = 10) and control pregnancies (N = 8) using a genome-wide approach with the Illumina® Infinium Human Methylation27 array, which interrogates 27,578 CpG sites. A total of 733 (2.7%) of the CpG sites were significantly differentially methylated between the 2 groups (P < 0.05), with an overall relative hypomethylation in the ART group (P < 0.001). Differences in DNA methylation were more pronounced for CpG sites in certain types of genomic locations and were related to baseline methylation levels and distance from CpG islands and transcription start sites. ART was associated with significantly higher variation in DNA methylation, suggesting that differences in DNA methylation between cases and controls may result from stochastic (or random) genome-wide changes in DNA methylation in ART pregnancies. We identified 24 candidate genes with 2 or more CpG sites that were significantly different between the IVF and control groups. The current study provides support for the hypothesis that ART or associated subfertility may be associated with genome-wide changes in DNA methylation, and these changes appear to be, at least in part, due to epigenetic instability in ART pregnancies. Further studies are required in order to determine the extent to which such ART-related epigenetic instability may have phenotypic consequences.

שפה מקוריתאנגלית
עמודים (מ-עד)474-483
מספר עמודים10
כתב עתEpigenetics
כרך10
מספר גיליון6
מזהי עצם דיגיטלי (DOIs)
סטטוס פרסוםפורסם - 1 ינו׳ 2015
פורסם באופן חיצוניכן

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