Abstract
To evaluate whether the genomic imprinting status of assistant reproductive technology (ART)-conceived offspring is stable. Prospective clinical observational study. Invitro fertilization (IVF) center, university-affiliated teaching hospital. Sixty ART-conceived babies (30 IVF and 30 intracytoplasmic sperm injection [ICSI]) and 60 naturally conceived babies. Collection of umbilical cord blood and peripheral blood samples. Expression profile was examined by microarray and real-time reverse-transcription polymerase chain reaction (PCR), allele-specific expression was studied by direct sequencing after PCR, and DNA methylation status was investigated by sodium bisulfite sequencing. Hierarchic clustering demonstrated no obvious clustering between the ART- and naturally conceived offspring, suggesting similar genomic imprinting expression between the two groups. Three differentially expressed genes were identified in ART-conceived offspring, with PEG10 and L3MBTL up-regulated and PHLDA2 down-regulated. Allele-specific expression of the differentially expressed imprinted genes was maintained in the majority of the ART- and naturally conceived offspring. However, in one ICSI case, monoallelic expression of L3MBTL was disrupted and all CpGs were completely unmethylated. These were not inherited from the parents. The global profile of imprinting is stable in children conceived through ART. However, imprinting of a few specific imprinted genes may be vulnerable in a fraction of ART-conceived children.
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