| Popis: |
Assisted Reproductive Technology (ART) includes an array of treatments designed to bypass fertility problems in both men and women in order to achieve conception. These methods vary from hormonal stimulation of follicular development and ovulation in women, to laboratory handling of both male and female gametes leading to fertilization. In the developed world 1–3% of all births are the result of ART. In recent years, concern has been raised about possible increases in the occurrence of rare genomic imprinting disorders in ART-conceived children. Studies suggest that the perturbations seen in these children could be associated with epigenetic disruption of chromosomal regions or epimutations. Genomic imprinting refers to the acquisition of a unique epigenetic profile in a small subset of genes during gametogenesis. These differential epigenetic marks in the gametes result in a parent-of-origin specific expression of these imprinted genes in the offspring. An important epigenetic mark involved in the imprinting process is DNA methylation, which takes place in the male and female germlines at very specific times during the development of gametes and involves a well-orchestrated expression of enzymes. This period of DNA methylation acquisition may be susceptible to perturbations resulting from gamete handling. Furthermore, genomic imprinting established in the germline must remain unaltered following fertilization of these gametes and throughout the life of the offspring, raising another possibility for ART-induced epigenetic disturbance during the maintenance of these imprints in early embryonic life. In the present chapter we discuss the current data available on the effects of ART on genomic imprinting in humans, as well as in animal research models, and discuss the possible mechanisms involved in this epigenetic deregulation. |
