DNA methylation errors in imprinting disorders and assisted reproductive technology

There have been increased incident reports of rare imprinting disorders associated with assisted reproductive technology (ART). ART is an important treatment for infertile people of reproductive age and is increasingly common. The identification of epigenetic changes at imprinted loci in ART infants has led to the suggestion that the techniques themselves may predispose embryos to acquisition of imprinting errors and disease. It is still unknown, however, at what point(s) these imprinting errors arise, or the risk factors. In this review it was hypothesized that the particular steps of the ART process may be prone to induction of imprinting methylation errors during gametogenesis, fertilization and early embryonic development. In addition, imprinting diseases and their causes are explained. Moreover, using a Japanese nationwide epidemiological study of imprinting diseases, their association with ART is determined. Epigenetic studies are required to understand the pathogenesis of this association; the ART-related risk factor(s); and the precautions that can be taken to prevent the occurrence of these syndromes. It is hoped that the constitution of children born after ART will indicate the safest and most ethical approach to use, which will be invaluable for the future development of standard ART treatment.