Gametes and embryo epigenetic reprogramming affect developmental outcome: implication for assisted reproductive technologies.

Abstract

There is concern about the health of children who are conceived with the use assisted reproductive technologies (ART). In addition to reports of low birth weight and chromosomal anomalies, there is evidence that ART may be associated with increased epigenetic disorders in the infants who are conceived using these procedures. Epigenetic reprogramming is critical during gametogenesis and at preimplantation stage and involves DNA methylation, imprinting, RNA silencing, covalent modifications of histones, and remodeling by other chromatin-associated complexes. Epigenetic regulation is involved in early embryo development, fetal growth, and birth weight. Disturbances in epigenetic reprogramming may lead to developmental problems and early mortality. Recent reports suggest the increased incidence of imprinting disorders such as Beckwith-Wiedemann syndrome, Angelman syndrome, and retinoblastoma in children who are conceived with the use of ART. These may result from an accumulation of epigenetic alterations during embryo culture and/or by altered embryonic developmental timing. Further research is urgently needed to determine whether a causal relationship between ART and epigenetic disorders exists. Until then, cautious review of both short-term and long-term ART outcomes at a national level is recommended.