DNA methylation reprogramming in human preimplantation development.

Epigenetic marks such as DNA methylation allow for gene expression regulation independent of the underlying DNA sequence. During the first days of embryonic development, there is genome-wide epigenetic reprogramming that is essential for further development. Studies on human and various animal models indicate that this epigenetic reprogramming might be hampered by external and environmental factors such as those present during assisted reproductive technologies (ART). Since most of our knowledge on reprogramming in embryos came from animal studies and species-specific differences in DNA (de)methylation kinetics had been suggested in literature, there was a need to investigate DNA methylation reprogramming during human preimplantation development. We therefore studied global DNA (de)methylation patterns together with their regulators, the DNA methyltransferases (DNMTs), in human oocytes, zygotes and embryos up to day 7 of in vitro preimplantation development. The data obtained from human good quality fresh embryos served as reference data in studies of poor quality embryos and in safety studies investigating the impact of oocyte or embryo cryopreservation on DNA methylation reprogramming. Appropriate DNA (hydroxy)methylation reprogramming was linked with good embryo quality up to the blastocyst stage. Global methylation patterns as well as DNMT expression patterns were disturbed in thawed embryos. The data that emerged from our experiments differed compared to the current model for DNA methylation reprogramming, largely based on mouse data, calling for an amendment of the model.