Suboptimal in vitro culture conditions: an epigenetic origin of long‐term health effects

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Abstract
The foetal origins of adult diseases or Barker hypothesis suggests that there can be adverse in uterus effects on the foetus that can lead to certain diseases in adults. Extending this hypothesis to the early stages of embryo development, in particular, to preimplantation stages, it was recently demonstrated that, long‐term programming of postnatal development, growth and physiology can be irreversibly affected during this period of embryo development by suboptimal in vitro culture (IVC). As an example, it was found in two recent studies that, mice derived from embryos cultured in suboptimal conditions can suffer from obesity, increased anxiety, and deficiencies on their implicit memory system. In addition, it was observed that suboptimal IVC can cause disease in mature animals by promoting alterations in their genetic imprinting during preimplantation development. Imprinting and other epigenetic mechanisms control the establishment and maintenance of gene expression patterns in the embryo, placenta and foetus. The previously described observations, suggest that the loss of epigenetic regulation during preimplantation development may lead to severe long‐term effects. Although mostly tested in rodents, the hypothesis that underlies these studies can also fit assisted reproductive technology (ART) procedures in other species, including humans. The lack of information on how epigenetic controls are lost during IVC, and on the long‐term consequences of ART, underscore the necessity for sustained epigenetic analysis of embryos produced in vitro and long‐term tracking of the health of the human beings conceived using these procedures. Mol. Reprod. Dev. 74: 1149–1156, 2007.