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DNA methylation differences at birth after conception through ART

Tobi, Elmar W. and Almqvist, Catarina and Hedman, Anna and Andolf, Ellika and Holte, Jan and Olofsson, Jan and Wramsby, Hakan and Wramsby, Margaretha and Pershagen, Goran and Heijmans, Bastiaan T. and Iliadou, Anastasia N. (2021). DNA methylation differences at birth after conception through ART. Human Reproduction. 36 , 248-259
[Research article]

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Abstract

STUDY QUESTION: Is there a relation between ART and DNA methylation (DNAm) patterns in cord blood, including any differences between IVF and ICSI?SUMMARY ANSWER: DNAm at 19 CpGs was associated with conception via ART, with no difference found between IVF and ICSI.WHAT IS KNOWN ALREADY: Prior studies on either IVF or ICSI show conflicting outcomes, as both widespread effects on DNAm and highly localized associations have been reported. No study on both IVF and ICSI and genome-wide neonatal DNAm has been performed.STUDY DESIGN, SIZE, DURATION: This was a cross-sectional study comprising 87 infants conceived with IVF or ICSI and 70 conceived following medically unassisted conception. The requirement for inclusion in the study was an understanding of the Swedish language and exclusion was the use of donor gametes.PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were from the UppstART study, which was recruited from fertility and reproductive health clinics, and the Born into Life cohort, which is recruited from the larger LifeGene study. We measured DNAm from DNA extracted from cord blood collected at birth using a micro-array (450k array). Group differences in DNAm at individual CpG dinucleotides (CpGs) were determined using robust linear models and post-hoc Tukey's tests.MAIN RESULTS AND THE ROLE OF CHANCE: We found no association of ART conception with global methylation levels, imprinted loci and meta-stable epialleles. In contrast, we identify 19 CpGs at which DNAm was associated with being conceived via ART (effect estimates: 0.5-4.9%, P-FDR < 0.05), but no difference was found between IVF and ICSI. The associated CpGs map to genes related to brain function/development or genes connected to the plethora of conditions linked to subfertility, but functional annotation did not point to any likely functional consequences.LIMITATIONS, REASONS FOR CAUTION: We measured DNAm in cord blood and not at later ages or in other tissues. Given the number of tests performed, our study power is limited and the findings need to be replicated in an independent study.WIDER IMPLICATIONS OF THE FINDINGS: We find that ART is associated with DNAm differences in cord blood when compared to non-ART samples, but these differences are limited in number and effect size and have unknown functional consequences in adult blood. We did not find indications of differences between IVF and ICSI.

Authors/Creators:Tobi, Elmar W. and Almqvist, Catarina and Hedman, Anna and Andolf, Ellika and Holte, Jan and Olofsson, Jan and Wramsby, Hakan and Wramsby, Margaretha and Pershagen, Goran and Heijmans, Bastiaan T. and Iliadou, Anastasia N.
Title:DNA methylation differences at birth after conception through ART
Series Name/Journal:Human Reproduction
Year of publishing :2021
Volume:36
Page range:248-259
Number of Pages:12
Publisher:OXFORD UNIV PRESS
ISSN:0268-1161
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 302 Clinical Medicine > Obstetrics, Gynaecology and Reproductive Medicine
Keywords:DNA methylation, ART, IVF, ICSI, epigenome-wide association study, cord blood, epigenetics
URN:NBN:urn:nbn:se:slu:epsilon-p-111998
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-111998
Additional ID:
Type of IDID
DOI10.1093/humrep/deaa253
Web of Science (WoS)000646859800025
ID Code:24318
Deposited By: SLUpub Connector
Deposited On:01 Jun 2021 07:03
Metadata Last Modified:01 Jun 2021 07:11

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