Alteration of Genomic Imprinting after Assisted Reproductive Technologies and Long-Term Health

Abstract

Assisted reproductive technologies (ART) are the treatment of choice for some infertile couples and even though these procedures are generally considered safe, children conceived by ART have shown higher reported risks of some perinatal and postnatal complications such as low birth weight, preterm birth, and childhood cancer. In addition, the frequency of some congenital imprinting disorders, like Beckwith–Wiedemann Syndrome and Silver–Russell Syndrome, is higher than expected in the general population after ART. Experimental evidence from animal studies suggests that ART can induce stress in the embryo and influence gene expression and DNA methylation. Human epigenome studies have generally revealed an enrichment of alterations in imprinted regions in children conceived by ART, but no global methylation alterations. ART procedures occur simultaneously with the establishment and maintenance of imprinting during embryonic development, so this may underlie the apparent sensitivity of imprinted regions to ART. The impact in adulthood of imprinting alterations that occurred during early embryonic development is still unclear, but some experimental evidence in mice showed higher risk to obesity and cardiovascular disease after the restriction of some imprinted genes in early embryonic development. This supports the hypothesis that imprinting alterations in early development might induce epigenetic programming of metabolism and affect long-term health. Given the growing use of ART, it is important to determine the impact of ART in genomic imprinting and long-term health.