PI3K inhibitor reduces in vitro maturation and developmental competence of porcine oocytes

Jiao, Yafei; Li, Jiaojiao; Zhu, Shaoqian; Ahmed, Jam Zaheer; Li, Mengmei; Shi, Dongquan; Huang, Bingqing

doi:10.1016/j.theriogenology.2020.08.019

Cited by 12 publications

(6 citation statements)

References 24 publications

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“…There is a large body of evidence concerning the association of AKT activity in CCs with the developmental competence of mammalian oocytes, and the involvement of specific genes controlled by PI3K/AKT kinase signaling in the regulation of various events in preovulatory follicles and in cultured COCs. The addition of the PDK1/PI3K/AKT activator PS48 into the culture medium increased the expansion of cumulus cells and the maturation rate of porcine oocytes [57]. Vice versa, PI3K/AKT inhibitors LY294002 and SH6 reduced the cumulus expansion and developmental competence of porcine and bovine oocytes assessed by blastocyst rate after parthenogenetic activation [38,58,59].…”

Section: Discussionmentioning

confidence: 99%

“…These phenotype changes were accompanied by substantial changes in the expression of specific genes in CCs as well as in mRNA abundance in the oocytes. The stimulation of AKT signaling led in matured oocytes to an increased mRNA abundance of genes involved in cell signaling and proliferation, such as cyclin B1, MOS, BMP15, GDF9 and CDC2, and to a decreased expression of pro-apoptotic genes such as BAX, BCL2 and caspase-3 [57]. Similarly, a melatonin-reversed inhibition of AKT by SH6 was associated in bovine COCs with an up-regulation of genes involved in cell signaling, mitochondrial function and cumulus expansion (GDF9, BMP15, ATPase, ATP5F1E, HAS2, TNFAIP6 and PTGS2) and downregulation of the pro-apoptotic genes [59].…”

Section: Discussionmentioning

confidence: 99%

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The Role of MAPK3/1 and AKT in the Acquisition of High Meiotic and Developmental Competence of Porcine Oocytes Cultured In Vitro in FLI Medium

Procházka

Bartková

Němcová

et al. 2021

IJMS

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The developmental potential of porcine oocytes cultured in vitro was remarkably enhanced in a medium containing FGF2, LIF and IGF1 (FLI) when compared to a medium supplemented with gonadotropins and EGF (control). We analyzed the molecular background of the enhanced oocyte quality by comparing the time course of MAPK3/1 and AKT activation, and the expression of genes controlled by these kinases in cumulus-oocyte complexes (COCs) cultured in FLI and the control medium. The pattern of MAPK3/1 activation in COCs was very similar in both media, except for a robust increase in MAPK3/1 phosphorylation during the first hour of culture in the FLI medium. The COCs cultured in the FLI medium exhibited significantly higher activity of AKT than in the control medium from the beginning up to 16 h of culture; afterwards a deregulation of AKT activity occurred in the FLI medium, which was not observed in the control medium. The expression of cumulus cell genes controlled by both kinases was also modulated in the FLI medium, and in particular the genes related to cumulus-expansion, signaling, apoptosis, antioxidants, cell-to-cell communication, proliferation, and translation were significantly overexpressed. Collectively, these data indicate that both MAPK3/1 and AKT are implicated in the enhanced quality of oocytes cultured in FLI medium.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Role of MAPK3/1 and AKT in the Acquisition of High Meiotic and Developmental Competence of Porcine Oocytes Cultured In Vitro in FLI Medium

Procházka

Bartková

Němcová

et al. 2021

IJMS

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“…Whether CARM1 is essential for blastocyst formation in mice has not reached consistent conclusions ( White et al, 2016 ; Yang et al, 2019 ), but our data document that CARM1 is indispensable for porcine blastocyst development. A number of signaling pathways have been shown to be essential for blastocyst formation in mammals ( Maekawa et al, 2005 ; Nakasato et al, 2006 ; Jiao et al, 2020 ). In this study, single-embryo transcriptomic analysis revealed that CARM1 is implicated in both Hippo and PI3K-AKT signaling pathways, in which amphiregulin ( AREG) was downregulated in CARM1 KD embryos.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies established that AREG peptide supplementation elevated blastocyst rates in mice ( Richani et al, 2013 ) and pigs ( Prochazka et al, 2011 ). In addition, inhibition of Akt activity blocked murine blastocyst formation ( Riley et al, 2005 ), and inactivation of PI3K signaling also prevented porcine blastocyst development ( Jiao et al, 2020 ). Together, these data demonstrate that CARM1 in porcine embryos facilitates blastocyst formation via modulating the expression of key genes involved in signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Histone Arginine Methyltransferase CARM1-Mediated H3R26me2 Is Essential for Morula-to-Blastocyst Transition in Pigs

Cao

Yin³

et al. 2021

Front. Cell Dev. Biol.

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Coactivator-associated arginine methyltransferase 1 (CARM1) is involved in both establishment of first pluripotent lineage and pluripotency maintenance of embryonic stem cells (ESCs) in mice. However, the histone substrates and role of CARM1 in early embryonic development remain largely unknown. Here, we show that CARM1 specifically catalyzes H3R26me2 to promote porcine blastocyst formation. The putative histone substrates of CARM1, including H3R2me2, H3R17me2, and H3R26me2, are present in pig early embryos. The changes of CARM1 mRNA during early embryogenesis parallel that of H3R26me2. Functional studies using a combinational approach of chemical inhibition and RNA interference (RNAi) showed that catalytic activity inhibition of CARM1 protein or knockdown (KD) of CARM1 mRNA did not alter the levels of both H3R2me2 and H3R17me2, but significantly reduced H3R26me2 levels in porcine embryos. Furthermore, CARM1 inhibition or KD did not affect embryo development to the 2-cell, 4-cell, 8-cell, and morula stages, but severely compromised blastocyst development. CARM1 knocked down embryos that developed to the blastocyst stage had fewer total cells, inner cell mass (ICM), and trophectoderm (TE) cells. Mechanistically, single embryo RNA-sequencing analysis revealed that CARM1 KD altered the transcriptome characterized by downregulation of key genes associated with Hippo and PI3K-AKT signaling pathways. Taken together, these results demonstrate that CARM1 specifically catalyzes H3R26me2 in porcine embryos and participates in blastocyst development.

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“…In addition, Akt is an important player in the regulation of apoptosis, in somatic cells Akt prevents the translocation of the BAX protein to the mitochondria to start apoptosis [57]. Akt is also involved in the control of apoptosis during meiosis, the elevation of Akt activity in matured oocytes led to an enhanced expression of genes involved in cell signaling and proliferation, and to a decreased expressions of pro-apoptotic genes such as BAX, BCL2 and caspase-3 [58]. It has been suggested that Akt could be involved in the regulation of the expression, activity and localization of pro-apoptotic proteins in oocytes and, moreover, AKT could stabilize endogenous apoptosis inhibitors [59].…”

Section: Meiosis Stage Akt Role In Meiosis Referencesmentioning

confidence: 99%

A Role of PI3K/Akt Signaling in Oocyte Maturation and Early Embryo Development

Kalous

Aleshkina

Anger

2023

Cells

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A serine/threonine-specific protein kinase B (PKB), also known as Akt, is a key factor in the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway that regulates cell survival, metabolism and proliferation. Akt phosphorylates many downstream specific substrates, which subsequently control the nuclear envelope breakdown (NEBD), centrosome maturation, spindle assembly, chromosome segregation, and cytokinesis. In vertebrates, Akt is also an important player during oogenesis and preimplantation development. In the signaling pathways regulating mRNA translation, Akt is involved in the control of mammalian target of rapamycin complex 1 (mTORC1) and thereby regulates the activity of a translational repressor, the eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1). In this review, we summarize the functions of Akt in mitosis, meiosis and early embryonic development. Additionally, the role of Akt in the regulation of mRNA translation is addressed with respect to the significance of this process during early development.

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PI3K inhibitor reduces in vitro maturation and developmental competence of porcine oocytes

Cited by 12 publications

References 24 publications

The Role of MAPK3/1 and AKT in the Acquisition of High Meiotic and Developmental Competence of Porcine Oocytes Cultured In Vitro in FLI Medium

The Role of MAPK3/1 and AKT in the Acquisition of High Meiotic and Developmental Competence of Porcine Oocytes Cultured In Vitro in FLI Medium

Histone Arginine Methyltransferase CARM1-Mediated H3R26me2 Is Essential for Morula-to-Blastocyst Transition in Pigs

A Role of PI3K/Akt Signaling in Oocyte Maturation and Early Embryo Development

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