Assisted reproductive technology alters deoxyribonucleic acid methylation profiles in bloodspots of newborn infants

作者：Estill Molly S; Bolnick Jay M; Waterland Robert A; Bolnick Alan D; Diamond Michael P; Krawetz Stephen A^*

来源：Fertility and Sterility, 2016, 106(3): 629-+.

DOI：10.1016/j.fertnstert.2016.05.006

• ART
• epialleles
• epigenetics
• ICSI
• 450k

Objective: To evaluate the effect of infertility and intracytoplasmic sperm injection (ICSI) on DNA methylation of offspring.
Design: Microarray analysis of DNA methylation in archived neonatal bloodspots of in vitro fertilization (IVF)/ICSI-conceived children compared with controls born to fertile and infertile parents.
Setting: Academic research laboratory.
Patient(s): : Neonatal blood spots of 137 newborns conceived spontaneously, through intrauterine insemination (IUI), or through ICSI using fresh or cryopreserved (frozen) embryo transfer.
Intervention(s): None.
Main Outcome Measure(s): The Illumina Infinium HumanMethylation450k BeadChip assay determined genome-wide DNA methylation. Methylation differences between conception groups were detected using a Bioconductor package, ChAMP, in conjunction with Adjacent Site Clustering (A-clustering).
Result(s): The methylation profiles of assisted reproductive technology and IUI newborns were dramatically different from those of naturally (in vivo) conceived newborns. Interestingly, the profiles of ICSI-frozen (FET) and IUI infants were strikingly similar, suggesting that cryopreservation may temper some of the epigenetic aberrations induced by IVF or ICSI. The DNA methylation changes associated with IVF/ICSI culture conditions and/or parental infertility were detected at metastable epialleles, suggesting a lasting impact on a child's epigenome.
Conclusion(s): Both infertility and ICSI alter DNA methylation at specific genomic loci, an effect that is mitigated to some extent by FET. The impact of assisted reproductive technology and/or fertility status on metastable epialleles in humans was uncovered. This study provides an expanded set of loci for future investigations on IVF populations.

• 出版日期2016-9-1