1. Assisted reproductive technology alters deoxyribonucleic acid methylation profiles in bloodspots of newborn infants.
- Author
-
Estill, Molly S., Bolnick, Jay M., Waterland, Robert A., Bolnick, Alan D., Diamond, Michael P., and Krawetz, Stephen A.
- Subjects
- *
INTRACYTOPLASMIC sperm injection , *REPRODUCTIVE technology , *DNA methylation , *FERTILIZATION in vitro , *NEWBORN infant physiology , *DNA microarrays , *INFERTILITY , *PATIENTS , *INFERTILITY treatment , *HUMAN artificial insemination , *BLOOD testing , *DNA , *EMBRYO transfer , *FERTILITY , *NEWBORN screening , *RESEARCH funding , *TREATMENT effectiveness , *CASE-control method , *OLIGONUCLEOTIDE arrays , *DIAGNOSIS - 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. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF