Metabolism of the viable mammalian embryo: quietness revisited.

This review examines the 'Quiet Embryo Hypothesis' which proposes that viable preimplantation embryos operate at metabolite or nutrient turnover rates distributed within lower ranges than those of their less viable counterparts. The 'quieter' metabolism consistent with this hypothesis is considered in terms of (i) 'functional' quietness; the contrasting levels of intrinsic metabolic activity in different cell types as a consequence of their specialized functions, (ii) inter-individual embryo/cell differences in metabolism and (iii) loss of quietness in response to environmental stress. Data are reviewed which indicate that gametes and early embryos function in vivo at a lower temperature than core body temperature, which could encourage the expression of a quiet metabolism. We call for research to determine the optimum temperature for mammalian gamete/embryo culture. The review concludes by examining the key role of reactive oxygen species, which can induce molecular damage, trigger a cellular stress response and lead to a loss of quietness.

DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status.

A complex combination of adult health-related disorders can originate from developmental events that occur in utero. The periconceptional period may also be programmable. We report on the effects of restricting the supply of specific B vitamins (i.e., B(12) and folate) and methionine, within normal physiological ranges, from the periconceptional diet of mature female sheep. We hypothesized this would lead to epigenetic modifications to DNA methylation in the preovulatory oocyte and/or preimplantation embryo, with long-term health implications for offspring. DNA methylation is a key epigenetic contributor to maintenance of gene silencing that relies on a dietary supply of methyl groups. We observed no effects on pregnancy establishment or birth weight, but this modest early dietary intervention led to adult offspring that were both heavier and fatter, elicited altered immune responses to antigenic challenge, were insulin-resistant, and had elevated blood pressure-effects that were most obvious in males. The altered methylation status of 4% of 1,400 CpG islands examined by restriction landmark genome scanning in the fetal liver revealed compelling evidence of a widespread epigenetic mechanism associated with this nutritionally programmed effect. Intriguingly, more than half of the affected loci were specific to males. The data provide the first evidence that clinically relevant reductions in specific dietary inputs to the methionine/folate cycles during the periconceptional period can lead to widespread epigenetic alterations to DNA methylation in offspring, and modify adult health-related phenotypes.

Embryo viability and metabolism: obeying the quiet rules.

BACKGROUND: It has been proposed that preimplantation embryo viability during culture and following embryo transfer is associated with a 'quiet' metabolism. Viable embryos may be better equipped to contend with damage to the genome, transcriptome and proteome, or they may possess less damage than non-viable embryos. METHODS: Much of the data for the quiet embryo hypothesis was obtained in the human and mouse. In this article, evidence is reviewed suggesting that the quiet hypothesis may equally be applied to reproduction in livestock, which can provide good models for the human. RESULTS: Data, particularly for the sheep and cow, suggest that a quiet metabolism during early embryo development is consistent with successful embryo development. Conversely, an 'active' metabolism is associated with sub-optimal outcomes in later life. CONCLUSIONS: The challenge is to identify the range of values for a given marker within which an embryo has a high chance of giving rise to healthy offspring. We also speculate on the ways in which such a metabolic profile might be encouraged and the implications for weight loss in obese women prior to conception.