All living cells rely on intermediary metabolism to maintain an adequate state of energetics. Considerable progress has been made over the last century in defining many of the pathways and regulatory mechanisms of intermediary metabolism. Following from this mechanistic understanding, much insight has been gained into how organisms modulate the metabolism of their various cell types to achieve energy homeostasis during different physiologic states and developmental stages. In mammals, the prenatal period is less well characterized in terms of energy metabolism, principally due to technical difficulties associated with the small size of and limited accessibility to samples. The initial stages of prenatal development, when there is rapid growth and striking morphologic changes, stand out as a particularly important period for investigating energy metabolism. Furthermore, the increasing utilization of in vitro fertilization techniques for human and domestic animal reproduction mandates a better understanding of early embryonic metabolism to improve culture conditions. This review will provide an overview of the current understanding of intermediary metabolism associated with energy production in the early murine embryo, the most fully characterized of mammalian embryos. Several approaches that have been used to investigate embryonic metabolism will be considered, with a special emphasis being given to recently introduced mutations affecting pathways implicated in energy homeostasis of the early embryo.
Substrate Utilization during Early EmbryogenesisSince the first reports of successful culture of rabbit embryos almost a century ago, much effort has been devoted to defining the substrates required for mammalian embryo viability and then characterizing how these substrates are utilized. Before considering studies investigating the metabolism of substrates in vitro, it is important to appreciate what is known about the substrates that are available to the embryo in vivo. The embryo begins life with an endowment of maternally provided substrates that are carried over from the oocyte. Unlike a number of vertebrate and invertebrate species, oocytes from many mammalian species, including the mouse, contain relatively limited amounts of glycogen or lipids (1). Mammalian oocytes do, however, have substantial stores of amino acids and protein. It has been estimated that the endogenous protein store within the one-cell mouse embryo could meet all of its energetic needs for the first several days of development (2). The observation that the murine embryo loses ϳ25% of its total protein content during the first 2-3 days of development indicates that endogenous protein is catabolized during early embryogenesis (3). Beyond the first several days of development, little is known about the relative amounts of endogenous substrates present in the embryo, and no studies have determined how these endogenous substrates are utilized.Studies of the female reproductive tract fluid in the mouse have identified a number of substrates that c...