DNA methylation status of imprinted H19 and KvDMR1 genes in human placentas after conception using assisted reproductive technology

Assisted reproductive technologies (ARTs), such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), are thought to destabilize genomic imprints. Previous studies examining the association between ART and aberrant DNA methylation have been inconclusive. The DNA methylation status of and was compared between newborns conceived through ART and those conceived naturally to evaluate the safety of ART. Placental tissues from 6 full-term, naturally conceived pregnancies (no gestational comorbidities) and six full-term ART pregnancies (no gestational complication) were collected. Genomic DNA (gDNA) and RNA were extracted from both groups. Real-time PCR was used to analyze the mRNA expression levels of and in the placenta for both groups. A whole-genome DNA methylation microarray was used to examine three placentas from full-term, naturally conceived pregnancies and three placentas from full-term IVF pregnancies. The expression level of in the IVF group was significantly higher than that in the natural pregnancy group, whereas the expression level of was significantly lower in the ART group than in the natural pregnancy group. Also, human ART manipulation resulted in placental gDNA methylation modifications. Conclusion: Abnormal methylation patterns were detected in phenotypically normal phenotype conceived by ART, which may occur due to imprinting errors in sperm/oocyte cells or side effects of embryo culture procedures. Further investigation is necessary to determine whether imprinted gene expression and DNA methylation can be regulated through other mechanisms. Assisted reproductive technology (ART); placenta; methylation; H19; KvDMR1.