Embryo Culture and Epigenetics

Abstract

During preimplantation development, major epigenetic reprogramming occurs, erasing gametic modifications, and establishing embryonic epigenetic modifications. Given the plasticity of these modifications, they are susceptible to disruption by assisted reproductive technologies, including embryo culture. The current state of evidence is presented for the effects of embryo culture on global DNA methylation and histone modifications, retroviral silencing, X-inactivation, and genomic imprinting. Several salient points emerge from the literature; that culture in the absence of other procedures can lead to epigenetic perturbations; that all media are suboptimal; and that embryo response to in vitro culture is stochastic. We propose that embryos adapt to the suboptimal environment generated by embryo culture, including epigenetic adaptations, and that "quiet" embryos may be the least epigenetically compromised by in vitro culture.

Long-lasting alterations to DNA methylation and ncRNAs could underlie the effects of fetal alcohol exposure in mice

“…Regardless of the potential for differences in blood alcohol levels achieved within and between the paradigms, the results obtained using these mouse models serve as an effective means to examine the long-term consequences of FAE to the developing brain at distinct time points (Clancy et al, 2001; Rice and Barone, 2000). Indeed, despite the aforementioned limitations, this research still advances the understanding of FASD because previous research into FASD has focused on cell lines, which are not appropriate for epigenetic experimentation, specifically in the case of genomic imprinting (Velker et al, 2012), and prior in vivo studies into the epigenetics of FASD have focused on whole embryo tissue (Liu et al, 2009). Ultimately, given these facts, we believe that our observations on adult whole-brain tissue are a substantial contribution to the literature and will help to focus future research into specific brain regions using the biomarkers identified.…”

Lessons from the one-carbon metabolism: passing it along to the next generation

“…Recently, concerns have been raised regarding a potential negative impact of aberrant epigenetic programming caused by assisted reproduction treatment on fetal growth and development. In fact, analysis of human embryos conceived by assisted reproduction has revealed epigenetic alterations (Market Velker et al, 2012). Even though infertility is usually an underlying issue, animal studies completed in normal fertile conditions also reveal epigenetic perturbations (Market Velker et al, 2012).…”

Cytoplasmic Inheritance Redux

“…The phenotypes observed in LOS are similar to those observed in BWS and significantly, epigenetic abnormalities of the same loci involved in BWS are observed in calves and sheep with LOS: KCNQ10T1 is hypomethylated with a corresponding increase in KCNQ10T1 expression and decrease in CDKN1C expression (Hori et al, 2010); and LOS sheep also exhibit loss of imprinting for the IGF2 gene (Young et al, 2001). The similarities in IVF-induced epigenetic errors between humans and animal models, where subfertility is not a confounding issue, suggest that manipulation of the early embryo can lead to epigenetic perturbations with potential long-term consequences for offspring (Paolini-Giacobino, 2007;Velker et al, 2012). There is an additional concern that IVF could result in subtle abnormalities that present later in life.…”