Protein kinase Akt2/PKBβ is involved in blastomere proliferation of preimplantation mouse embryos

Abstract

Activation of Akt/Protein Kinase B (PKB) by phosphatidylinositol-3-kinase (PI3K) controls several cellular functions largely studied in mammalian cells, including preimplantation embryos. We previously showed that early mouse embryos inherit active Akt from oocytes and that the intracellular localization of this enzyme at the two-cell stage depends on the T-cell leukemia/lymphoma 1 oncogenic protein, Tcl1.We have now investigated whether Akt isoforms, namely Akt1, Akt2 and Akt3, exert a specific role in blastomere proliferation during preimplantation embryo development. We show that, in contrast to other Akt family members, Akt2 enters male and female pronuclei of mouse preimplantation embryos at the late one-cell stage and thereafter maintains a nuclear localization during later embryo cleavage stages.Depleting one-cell embryos of single Akt family members by microinjecting Akt isoform-specific antibodies into wild-type zygotes, we observed that: (a) Akt2 is necessary for normal embryo progression through cleavage stages; and (b) the specific nuclear targeting of Akt2 in two-cell embryos depends on Tcl1. Our results indicate that preimplantation mouse embryos have a peculiar regulation of blastomere proliferation based on the activity of the Akt/PKB family member Akt2, which is mediated by the oncogenic protein Tcl1. Both Akt2 and Tcl1 are essential for early blastomere proliferation and embryo development. K E Y W O R D SAkt/PKB isoforms, Akt2, mouse preimplantation embryos, Tcl1

Nicotinamide Supplementation during the In Vitro Maturation of Oocytes Improves the Developmental Competence of Preimplantation Embryos: Potential Link to SIRT1/AKT Signaling

“…This matches with the study of Chong et al that showed an enhancement of neural cell survival following administration of NAM under anoxia conditions through activating the AKT signaling that consequently reduced apoptosis [53]. Moreover, PI3K/AKT/mTOR signaling has a significant role in the development, metabolism, and pluripotency fate of cells [22,24,25] via modulating different transcription factors such as OCT4, SOX2, GATA4 and GATA6 [34,35]. OCT4 is the master controller of lineage specification of ICM [54] and for embryonic lineage-specific markers including SOX2 and GATA6.…”

“…SIRT1 exhibits its cellular activities via the transcription of various enzymes and signaling pathways including serine/threonine-specific protein kinase B (AKT) and mTOR [ 19 ]. On the other hand, the phosphatidylinositol 3-kinase (PI3K) and its downstream effectors AKT and mTOR regulate various cellular processes including apoptosis, development, proliferation, survival, and maintenance of pluripotency of embryos and stem cells [ 22 , 23 , 24 , 25 , 26 ]. PI3K mediates the activation of AKT at the Thr308 phosphorylation site via recruitment of phosphoinositide dependent kinase 1 (PDK1), whereas PDK1 can indirectly activate AKT at the Ser473 phosphorylation site by activating the rictor–mTOR complex 2 [ 27 ].…”

“…PI3K mediates the activation of AKT at the Thr308 phosphorylation site via recruitment of phosphoinositide dependent kinase 1 (PDK1), whereas PDK1 can indirectly activate AKT at the Ser473 phosphorylation site by activating the rictor–mTOR complex 2 [ 27 ]. During oocyte maturation and embryo development, the role of PI3K/AKT/mTOR signaling and its modulation by SIRT1 were previously investigated [ 19 , 22 , 23 , 24 ].…”

Changes in Oviductal Cells and Small Extracellular Vesicles miRNAs in Pregnant Cows

“…Additionally, PI3K/AKT pathway can mediate cell growth and survival in pre-implantation embryos. In early mouse embryos, PI3K-Akt subunits are expressed from zygote to blastocyst stage and are involved with blastomere proliferation (75,76). In bovine pre-implantation embryos, the activation PI3K signaling is also required for apoptosis control (71).…”

scGET: Predicting Cell Fate Transition During Early Embryonic Development by Single-Cell Graph Entropy

“…However, some non-differential genes may also be involved in the key biological activities of cells and play important roles in embryonic development [50] , [51] . As illustrated by functional analysis, the up-regulated expression of some key genes in MAPK and PI3K/Akt signaling pathways, both of which are essential for cell proliferation and differentiation [52] , [53] , results from the synergy of dark genes and their downstream targets. Thus, some dark genes such as IGF1 encoding growth factor and LAMC2 and COL4A1 encoding ECM are identified as upstream regulators for cell proliferation and may also be involved in other development processes.…”