title: Abnormal methylation patterns at the IGF2/H19 imprinting control region in phenotypically normal babies conceived by assisted reproductive technologies.
abstract: OBJECTIVE
  To evaluate epigenetic risks linked to assisted reproductive technologies (ART) by determining the methylation status of the IGF2/H19 imprinting control region (ICR) in offspring born after ART.
  
  
  METHODS
  A combined bisulfite restriction analysis (COBRA) and sequencing technique were used to determine the methylation status of the IGF2/H19 ICR in 61 phenotypically normal newborns conceived by ART. Thirty naturally conceived newborns were studied as controls.
  
  
  RESULTS
  There was no significant difference in methylation between ART newborns and naturally conceived newborns (46.7 ± 8.2% vs. 48.5 ± 8.7%, p>0.05). Abnormal demethylation patterns of the IGF2/H19 ICR were found in three dizygotic twins conceived by intracytoplasmic sperm injection (ICSI), but all three were phenotypically normal, and their sibling twins exhibited normal methylation patterns.
  
  
  CONCLUSIONS
  We hypothesize that the aberrant methylation patterns probably resulted from imprinting errors of paternal gametes or from in vitro embryo culture. Further investigation to determine whether gene expression can be regulated by other mechanisms in addition to DNA methylation would be beneficial.
authors.affiliation: Center for Reproductive Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, People's Republic of China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Shi
authors.forename: Yunping
authors.initials: Y
authors.lastname: Ni
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zheng
authors.forename: Shiling
authors.initials: S
authors.lastname: Chen
authors.forename: Mei
authors.initials: M
authors.lastname: Zhong
authors.forename: Fangrong
authors.initials: F
authors.lastname: Wu
authors.forename: Rong
authors.initials: R
authors.lastname: Xia
authors.forename: Yanqun
authors.initials: Y
authors.lastname: Luo
mesh_terms: D019175:DNA Methylation; D015252:Deoxyribonucleases, Type II Site-Specific; D018392:Genomic Imprinting; D006801:Humans; D007231:Infant, Newborn; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D027724:Reproductive Techniques, Assisted / Q000009:adverse effects*
chemical_list: C094335:H19 long non-coding RNA; C035170:IGF2 protein, human; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II; D015252:Deoxyribonucleases, Type II Site-Specific; C027046:TCGA-specific type II deoxyribonucleases