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.
Highlights
This review summarises epidemiological evidence of phenotypic alterations in individuals conceived by Assisted reproductive technologies (ART) and experimental evidence of the impact of the stress induced by ART in embryonic development
Large postnatal studies in children conceived by ART revealed increased risk to cerebral palsy [25] and no increased risk of autism spectrum disorders [25–30]
The identification of DNA methylation changes induced by ART could be problematic with small sample size, methylation assays with low sensitivity and low number of probes per region, and bioinformatic pipelines designed for other purposes
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Estimations suggest that the decline will continue and the fertility rate will be below the replacement rate by 2060 [1,2] The causes of this decline are multiple including new life style choices [3], and an increased rate of infertility [4]. Some studies have suggested an association between some environmental stressors (like pesticides, diet, stress, smoking, pollution, and BMI) and sperm count decline, menstrual cycle alterations, and abnormal oocyte maturation [6–14]. In this context, assisted reproductive technologies (ART) may become the preferred option for many infertile couples. Current knowledge of the potential influence of genomic imprinting alterations induced by ART in postnatal growth and development and risks of long-term health conditions is summarised
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