Medically assisted reproductive technologies (ARTs), such as in vitro embryo production, are increasingly being used to palliate infertility. Eggs are produced following a hormonal regimen that stimulates the ovaries to produce a large number of oocytes. Collected oocytes are then fertilized in vitro and allowed to develop in vitro until they are either frozen or transferred to mothers. There are controversial reports on the adverse impacts of these technologies on early embryos and their potential long-term effects. Using newly developed technological platforms that enable global gene expression and global DNA methylation profiling, we evaluated gene perturbations caused by such artificial procedures. We know that cells in the early embryo produce all cells in the body and are able to respond to their in vitro environment. However, it is not known whether gene perturbations are part of a normal response to the environment or are due to distress and will have long-term impacts. Although the mouse is an established genetic model used for quality control of culture media in clinics, the bovine is a large mono-ovulating mammal with similar embryonic kinetics as humans during the studied developmental window. These model systems are critical to understand the effects of assisted reproduction without the confounding impact of infertility and without the limitations imposed by the scarcity of donated human samples. The data obtained through our Bovine transcriptomic array and DNA methylation array indicate a progressive disruption of gene expression and methylation (both hyper and hypo methylation sites as the time spent in vitro increases. Other culture stress like glucose also affect gene expression and methylation in gene and telomere regions creating a specific pattern which mimics cancer cells. These results demonstrate that the in vitro environment has a significant impact on embryos at the transcriptomic level and at the DNA methylation level.
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