Abstract
Early life periconceptional exposures during assisted reproductive technology (ART) procedures could alter the DNA methylation profiles of ART children, notably in imprinted genes and repetitive elements. At the genome scale, DNA methylation differences have been reported in ART conceptions at birth, but it is still unclear if those differences remain at childhood. Here, we performed an epigenome-wide DNA methylation association study using Illumina InfiniumEPIC BeadChip to assess the effects of the mode of conception on the methylome of buccal cells from 7- to 8-year-old children (48 children conceived after ART or naturally (control, CTL)) and according to the embryo culture medium in which they were conceived. We identified 127 differentially methylated positions (DMPs) and 16 differentially methylated regions (DMRs) (FDR < 0.05) with low delta beta differences between the two groups (ART vs. CTL). DMPs were preferentially located inside promoter proximal regions and CpG islands and were mostly hypermethylated with ART. We highlighted that the use of distinct embryo culture medium was not associated with DNA methylation differences in childhood. Overall, we bring additional evidence that children conceived via ART display limited genome-wide DNA methylation variation compared with those conceived naturally.
Highlights
Assisted reproductive technologies (ARTs) have been in use for more than 40 years.They are clinically effective thanks to the improvement of diverse procedures, such as conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI)
To address the gaps in knowledge, we performed an epigenome-wide association study assessing more than 740,000 CpGs and CpHs using EPIC BeadChip on ART and non-ART children, and we evaluated the impact of the culture medium composition
We investigated whether ART procedures could affect the buccal cell methylome in non-imprinted and non-repetitive element regions, seeing as imprinted genes and repetitive elements were already explored in this dataset [28]
Summary
Assisted reproductive technologies (ARTs) have been in use for more than 40 years. They are clinically effective thanks to the improvement of diverse procedures, such as conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). ARTs are commonly used, it is estimated that children born by ART worldwide represent approximately 4% of all births [1]. Major adverse perinatal outcomes were first reported following ART including increased risk of preterm birth, and low and very low birthweight [2,3]. Epidemiological studies with more extensive follow-up have been performed, and they support that the majority of ART-conceived children are healthy, even though higher cardiometabolic risk profiles exist in ART offspring [4,5,6]. Potential long-term health risks, including malignances, associated with ART are still unknown in humans and might not be negligible [6,7]
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