Blastocyst metabolism

Abstract

The mammalian blastocyst exhibits an idiosyncratic metabolism, reflecting its unique physiology and its ability to undergo implantation. Glucose is the primary nutrient of the blastocyst, and is metabolised both oxidatively and through aerobic glycolysis. The production of significant quantities of lactate by the blastocyst reflects specific metabolic requirements and mitochondrial regulation; it is further proposed that lactate production serves to facilitate several key functions during implantation, including biosynthesis, endometrial tissue breakdown, the promotion of new blood vessel formation and induction of local immune-modulation of the uterine environment. Nutrient availability, oxygen concentration and the redox state of the blastocyst tightly regulate the relative activities of specific metabolic pathways. Notably, a loss of metabolic normality is associated with a reduction in implantation potential and subsequent fetal development. Even a transient metabolic stress at the blastocyst stage culminates in low fetal weights after transfer. Further, it is evident that there are differences between male and female embryos, with female embryos being characterised by higher glucose consumption and differences in their amino acid turnover, reflecting the presence of two active X-chromosomes before implantation, which results in differences in the proteomes between the sexes. In addition to the role of Hypoxia-Inducible Factors, the signalling pathways involved in regulating blastocyst metabolism are currently under intense analysis, with the roles of sirtuins, mTOR, AMP-activated protein kinase and specific amino acids being scrutinised. It is evident that blastocyst metabolism regulates more than the production of ATP; rather, it is apparent that metabolites and cofactors are important regulators of the epigenome, putting metabolism at centre stage when considering the interactions of the blastocyst with its environment.

Long term effects of ART: What do animals tell us?

“…Concomitantly, oxygen consumption increases greatly, and mitochondria become more active. It is worth noting that at the blastocyst stage, the ICM, and trophectoderm cells differ in their carbohydrate metabolism with trophectoderm cells oxidizing about half of the consumed glucose when ICM cells are exclusively glycolytic (Gardner & Harvey, ). Such an areobic glycolysis (Warburg Effect) makes glucose available for being used in the pentose phosphate pathway, generating biomolecules such as ribose moieties that are necessary for DNA and RNA synthesis and NADPH required for the synthesis of lipids and complex biomolecules.…”

Metabolic switching and cell fate decisions: implications for pluripotency, reprogramming and development

“…Energy-generating pathways are highly dynamic and metabolic fluxes vary dramatically across different cell types and tissues in response to developmental signals [6], nutritional status [7], environmental signals [8] and disease pathogenesis [9]. Metabolic flux is finely tuned to maximize function in different cell types and is linked to cell identity just as gene expression, epigenetics and morphology are.…”

Metabolite availability as a window to view the early embryo microenvironment in vivo

“…The “quiet” metabolism of embryos shifts from oxidative phosphorylation to glycolysis during the morula and blastocyst stages—particularly in cells of the inner cell mass, whereas trophoblasts consume much more oxygen (Houghton, ; reviewed by Gardner and Harvey, ). This metabolic characteristic, first discovered by Otto Warburg in tumors (Warburg, ), is shared by proliferating cells (Heiden, Cantley, & Thompson, ; Lunt & Vander Heiden, ) and persists through later embryonic stages (Krisher & Prather, ; Redel et al, ; Smith & Sturmey, ), although the increasing population of oxidative phosphorylation‐utilizing trophoblasts could account for the net increase in oxygen consumption reported between the morula and blastocyst stages (Kurosawa et al, ).…”

“…Indeed, oxygen concentration in the female reproductive tract changes dynamically, and may increase locally during implantation, possibly in response embryonic signaling to the female tissue. Considering that trophoblasts are more reliant on oxidative phosphorylation than cells of the inner cell mass (Gardner & Harvey, ; Houghton, ), blastocyst health overall may benefit from 5% rather than 2% oxygen.…”