Metabolism of the preimplantation embryo: 40 years on.

This review considers how our understanding of preimplantation embryo metabolism has progressed since the pioneering work on this topic in the late 1960s and early 1970s. Research has been stimulated by a desire to understand how metabolic events contribute to the development of the zygote into the blastocyst, the need for biomarkers of embryo health with which to improve the success of assisted conception technologies, and latterly by the 'Developmental Origins of Health and Disease' (DOHaD) concept. However, arguably, progress has not been as great as it might have been due to methodological difficulties in working with tiny amounts of tissue and the low priority assigned to fundamental research on fertility and infertility, with developments driven more by technical than scientific advances. Nevertheless, considerable progress has been made in defining the roles of the traditional nutrients: pyruvate, glucose, lactate, and amino acids; originally considered as energy sources and biosynthetic precursors, but now recognized as having multiple, overlapping functions. Other nutrients; notably lipids, are beginning to attract the attention they deserve. The pivotal role of mitochondria in early embryo development and the DOHaD concept, and in providing a cellular focus for metabolic events is now recognized. Some unifying ideas are discussed; namely 'stress-response models' and the 'quiet embryo hypothesis'; the latter aiming to relate the metabolism of individual preimplantation embryos to their subsequent viability. The review concludes by updating the state of knowledge of preimplantation embryo metabolism in the early 1970s and listing some future research questions.