Abstract
BackgroundWe, and others, have demonstrated previously that there are differences in DNA methylation and transcript levels of a number of genes in cord blood and placenta between children conceived using assisted reproductive technologies (ART) and children conceived in vivo. The source of these differences (the effect of ART versus the underlying infertility) has never been determined in humans. In this study, we have attempted to resolve this issue by comparing placental DNA methylation levels at 37 CpG sites in 16 previously identified candidate genes in independent populations of children conceived in vivo (‘fertile control’ group) with ART children conceived from two groups: either autologous oocytes with infertility in one or both parents (‘infertile ART’ group) or donor oocytes (obtained from young fertile donors) without male infertility (‘donor oocyte ART’ group).ResultsOf the 37 CpG sites analyzed, significant differences between the three groups were found in 11 CpGs (29.73 %), using ANOVA. Tukey’s post hoc test on the significant results indicated that seven (63.63 %) of these differences were significant between the donor oocyte ART and fertile control groups. In addition, 20 of the 37 CpGs analyzed had been identified as differentially methylated between ART and fertile control groups in an independent population in a prior study. Of these 20 CpG sites, 9 also showed significant differences in the present population. An additional 9 CpGs were found to be significantly different between the two groups. Of these 18 candidate CpGs, 12 CpGs (in seven candidate genes) also showed significant differences in placental DNA methylation levels between the donor oocyte ART and fertile control groups.ConclusionsThese data suggest strongly that the DNA methylation differences observed between ART and in vivo conceptions are associated with some aspect of ART protocols, not simply the underlying infertility.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-015-0071-7) contains supplementary material, which is available to authorized users.
Highlights
We, and others, have demonstrated previously that there are differences in DNA methylation and transcript levels of a number of genes in cord blood and placenta between children conceived using assisted reproductive technologies (ART) and children conceived in vivo
Modest but significant differences in DNA methylation have been identified between children conceived in vivo and children conceived by assisted reproductive technology (ART) [1,2,3,4,5,6,7,8,9,10]
We compared placental DNA methylation in children conceived in vivo with ART children conceived following fertilization of oocytes from two distinct groups: 1) autologous oocytes with infertility in one or both parents; 2) donor oocytes without male factor infertility in the recipient’s partner
Summary
Others, have demonstrated previously that there are differences in DNA methylation and transcript levels of a number of genes in cord blood and placenta between children conceived using assisted reproductive technologies (ART) and children conceived in vivo. The source of these differences (the effect of ART versus the underlying infertility) has never been determined in humans. Modest but significant differences in DNA methylation have been identified between children conceived in vivo and children conceived by assisted reproductive technology (ART) [1,2,3,4,5,6,7,8,9,10]. As the number of children born following ART continues to increase, it is critical to understand whether epigenetic changes are responsible for some of the adverse outcomes observed following ART
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