The embryonic environment can induce permanent changes in metabolism and increase disease risk in adults. Rodent models show that modifications in maternal diet exclusively during pre-implantation development can induce metabolic disease in adults. Changes must therefore occur within the early embryo and be maintained throughout development. Determining adaptive mechanisms is challenging due to the size of the early embryo. We generated ES cells from inbred C57BL/6 mice as a model to overcome these problems.
Methods: ES cell lines were derived from blastocysts of C57BL/6 mice assigned to either an isocaloric low protein diet (LPD), or a control diet exclusively through pre-implantation development. Lines were characterised for karyotype, sex, gene expression, and functional characteristics including proliferation and death at standardised passages.
Results: LPD had no impact on blastocyst formation in vivo. Although LPD blastocyst outgrowth was comparable, there was a significant reduction in the capacity for ES cell derivation. While the ES cell lines retained similar levels of gene expression related to pluripotency, and developmental functions irrespective of diet, LPD cells showed increased basal apoptosis, and reduced phosphorylated ERK kinase.
Discussion: The reduced ES cell isolation efficiency may indicate an increased sensitivity of maternal LPD ES cells to apoptotic stimuli. ERK-mediated survival signalling may underlie this. Such adaptations in the early embryo may impact on lineage allocation as differentiation occurs. These ES cell lines may provide a model to investigate such mechanistic adaptations in post-implantation tissues providing insight into foetal responses to poor nutrition and the induction of adult onset disease.
02 Sep 2014 - 04 Sep 2014