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

Authors: Estill, Molly S; Bolnick, Jay M; Waterland, Robert A; Bolnick, Alan D; Diamond, Michael P; Krawetz, Stephen A

Published In Fertil Steril, (2016 09 01)

Abstract: 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.

PubMed ID: 27288894 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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