New insights into human pre-implantation metabolism in vivo and in vitro
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REVIEW
New insights into human pre-implantation metabolism in vivo and in vitro Yves Ménézo & Isabelle Lichtblau & Kay Elder
Received: 4 December 2012 / Accepted: 28 January 2013 # Springer Science+Business Media New York 2013
Abstract The metabolism of pre-implantation embryos is far from being understood. In human embryos, the two major obstacles are the scarcity of material, for obvious ethical reasons, and complete absence of a relevant in vivo control model. Over-extrapolation from animal species to human systems adds to the complexity of the problem. Removal of some metabolites from media has been proposed, such as glucose and essential amino acids, on the basis of their pseudo “toxicity”. In contrast, addition of some compounds such as growth factors has been proposed in order to decrease apoptosis, which is a natural physiologic process. These suggestions reflect the absence of global knowledge, and in
consequence mask reality. Some aspects of metabolism have been ignored, such as lipid metabolism. Others are seriously underestimated, such as oxidative stress and its relationship to imprinting/methylation, of paramount importance for genetic regulation and chromosomal stability. It has become increasingly obvious that more studies are essential, especially in view of the major extension of ART activities worldwide. Keywords Human embryo . Metabolism . Imprinting . Oxidative stress . Culture medium
Introduction Capsule Knowledge of human embryo metabolism is complicated by the complete lack of an in vivo model. Metabolic variations between animal models and human systems are evident. We have attempted to add to current knowledge by interpreting information yielded via mRNA transcripts found in the oocyte. We have re-evaluated metabolism of lipids, glucose and amino acids, with a special focus on oxidative stress, imprinting and apoptosis, since certain physiological aspects have not previously been taken into account. More studies are essential in order to avoid introducing artifacts that bypass physiological processes and mask the biochemistry involved in real-time metabolism. Y. Ménézo (*) Laboratoire CLEMENT, 17 avenue d’Eylau, 75016 Paris, France e-mail: [email protected] Y. Ménézo London Fertility Associates, Harley Street, London, UK I. Lichtblau Clinique de la Muette, Rue Nicolo, 75016 Paris, France e-mail: [email protected] K. Elder Bourn Hall Clinic, Cambridge CB3 2TN, UK e-mail: [email protected]
The goal of in-vitro fertilization (IVF) and embryo culture is to provide high quality embryos capable of continued development and implantation that will result in the birth of healthy babies. The early studies of pre-implantation embryo in vitro culture were conducted in animal systems [1–6], and considerable progress has been made since these were undertaken. During the early 70s, we and other teams [7] began to design and define new, more complex culture media, which were based on the composition of genital tract secretions [8]. During the initial stages of zygote formation and
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