Genomic methylation occurs in a cyclical fashion in mammals. Genomic imprints are erased and re-established during gametogenesis but re-establishment of methylation occurs much later in the development of oocytes. In spermatogenesis remethylation primarily occurs prior to birth, whereas in oogenesis remethylation begins after birth (a) and is not completed until metaphase of meiosis II [15]. This time (b) will vary for each oocyte and can last from birth until menopause. Once fertilization (c) occurs each haplogenome will again undergo demethylation, actively in the male haplogenome (d) and passively in the female haplogenome (e). Remethylation of the zygotic genome will then occur around the time of implantation (f) [15]. Assisted reproductive technology (ART) procedures occur during these vulnerable developmental periods and have been proposed to interact at certain points of the methylation cycle (g, ovulation induction and egg retrieval; h, IVF, ICSI, micromanipulation of gametes, exposure to culture medium, preimplantation genetic diagnosis, in-vitro oocyte maturation).
, baseline methylation; - - - -, male haplogenome; – – – –, female haplogenome.