DNA methylation in newborns conceived by assisted reproductive technology

Siri E. Håberg (), Christian M. Page, Yunsung Lee, Haakon E. Nustad, Maria C. Magnus, Kristine L. Haftorn, Ellen Ø. Carlsen, William R. P. Denault, Jon Bohlin, Astanand Jugessur, Per Magnus, Håkon K. Gjessing and Robert Lyle
Additional contact information
Siri E. Håberg: Norwegian Institute of Public Health
Christian M. Page: Norwegian Institute of Public Health
Yunsung Lee: Norwegian Institute of Public Health
Haakon E. Nustad: Norwegian Institute of Public Health
Maria C. Magnus: Norwegian Institute of Public Health
Kristine L. Haftorn: Norwegian Institute of Public Health
Ellen Ø. Carlsen: Norwegian Institute of Public Health
William R. P. Denault: Norwegian Institute of Public Health
Jon Bohlin: Norwegian Institute of Public Health
Astanand Jugessur: Norwegian Institute of Public Health
Per Magnus: Norwegian Institute of Public Health
Håkon K. Gjessing: Norwegian Institute of Public Health
Robert Lyle: Norwegian Institute of Public Health

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Assisted reproductive technology (ART) may affect fetal development through epigenetic mechanisms as the timing of ART procedures coincides with the extensive epigenetic remodeling occurring between fertilization and embryo implantation. However, it is unknown to what extent ART procedures alter the fetal epigenome. Underlying parental characteristics and subfertility may also play a role. Here we identify differences in cord blood DNA methylation, measured using the Illumina EPIC platform, between 962 ART conceived and 983 naturally conceived singleton newborns. We show that ART conceived newborns display widespread differences in DNA methylation, and overall less methylation across the genome. There were 607 genome-wide differentially methylated CpGs. We find differences in 176 known genes, including genes related to growth, neurodevelopment, and other health outcomes that have been associated with ART. Both fresh and frozen embryo transfer show DNA methylation differences. Associations persist after controlling for parents’ DNA methylation, and are not explained by parental subfertility.

Date: 2022
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DOI: 10.1038/s41467-022-29540-w

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