Glucose utilization and the PI3-K pathway: mechanisms for cell survival in preimplantation embryos

Abstract

The maintenance of optimal glucose utilization during the preimplantation period is critical for embryo survival. A decrease in glucose transport during preimplantation development has been linked to the early steps of programmed cell death in these embryos. Decreased glucose transport is not thought to be simply a consequence of cell death, rather it is thought to be a trigger that can initiate the apoptotic cascade. Extensive apoptosis during the preimplantation period may manifest later in pregnancy as a malformation -or miscarriage, if cell loss is excessive. Phosphatidylinositol 3-kinase (PI3-K) is a known regulator of a number of physiologic responses including cellular proliferation, growth, and survival as well as glucose metabolism. Studies performed in other cell systems have demonstrated that the PI3-K pathway plays a critical role in maintaining glucose transport and metabolism. This review will present the current evidence that suggests that PI3-K is vital for preimplantation embryo survival and development. In addition, data demonstrating that PI3-K activity is important for glucose metabolism during this early developmental period will be discussed.

Preimplantation Embryo Development in the Mouse Requires the Latency of TRP53 Expression, Which Is Induced by a Ligand-Activated PI3 Kinase/AKT/MDM2-Mediated Signaling Pathway1

“…Autocrine signals induce receptor-mediated activation of PI3 kinase [28,29,41]. PI3 kinase induces the phosphorylation of membrane inositol phospholipids, resulting in the formation of D-3 0 phosphoinositides.…”

Discovery of candidate genes and pathways in the endometrium regulating ovine blastocyst growth and conceptus elongation

“…Of particular note, transporters for glucose (SLC2A9, SLC5A1) and glucose and fructose (SLC2A5) were upregulated between days 9 and 12 of pregnancy. Glucose is the main substrate used by mammalian embryos as a source of energy and can be utilized anabolically to synthesize glycogen, nucleic acids, proteins, and lipids (69). In ewes, the amount of glucose in the uterine lumen increases sixfold between days 10 and 15 of gestation (22).…”

Regulation of Facilitative Glucose Transporters and AKT/MAPK/PRKAA Signaling via Estradiol and Progesterone in the Mouse Uterine Epithelium1

“…Thirteen members of the GLUT (SLC2A) family have been subdivided into three classes: class I consists of SLC2As 1, 2, 3, and 4; class II consists of SLC2As 5, 7, 9, and 11; and class III consists of SLC2As 6, 8, 10, and 12 and the H þ -coupled myoinositol transporter [1][2][3]. GLUTs exhibit a high degree of sequence homology; however, they differ in their substrate specificity, kinetic characteristics, tissue and subcellular distribution, and response to extracellular stimuli [1,4].…”