Ganglioside GM3 induces cumulus cell apoptosis through inhibition of epidermal growth factor receptor‐mediated PI3K/AKT signaling pathways during in vitro maturation of pig oocytes

Park, Hyo-Jin; Chae, Sung-Kyu; Kim, Jin-Woo; Yang, Seul‐Gi; Jung, Jaemin; Kim, Minji; Wee, Gabbine; Lee, Dong Seok; Kim, Sun-Uk; Koo, Deog‐Bon

doi:10.1002/mrd.22848

Cited by 23 publications

(21 citation statements)

References 32 publications

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“…Similarly, GM3 inhibits c-fos and c-jun expression, and thus consequently the inhibition of c-fos and c-jun by GM3 is consistent with the inhibition of MAP kinase activity by GM3 [84]. Additionally, Park et al [36] showed that in porcine cumulus-oocyte complexes (COCs), exogenous GM3 inhibits meiotic maturation and restricts the expansion of cumulus cells during in vitro meiotic maturation through EGFR-mediated PI3K/AKT signaling pathways and initiates apoptosis (Figure 3). GM3 also works and shows increased apoptosis in human colon cancer [85] and murine bladder cancer [34].…”

Section: Gangliosides On Oocytes and Preimplantation Embryossupporting

confidence: 56%

“…Continuous mitochondrial regulation releases pro-apoptotic proteins such as cytochrome c into the cytoplasm causing caspase cascades processed by apoptosis, the programed cell death [52].The most compelling evidence shows that GM3 treatment decreases phosphorylated EGFR levels and regulates down-stream EGFR activation in cumulus-oocyte complexes COCs. Consequently, GM3 exposure reduces EGFR-delivered PI3K/AKT signaling for proliferation during in vitro maturation of porcine COCs [36].…”

Section: Gangliosides On Oocytes and Preimplantation Embryosmentioning

confidence: 99%

“…GM3 also inhibits the tyrosine kinase activity of the EGFR in hepatoma cells [35] and induces cumulus cell apoptosis during in vitro maturation (IVM) of porcine oocytes. [36]. However, the growth of Siat9 (encoding GM3 synthase) and Galgt1 (encoding GM2 synthase)-deficient knock out cancer cells is strongly impeded both in vivo and vitro [37].…”

Section: Introductionmentioning

confidence: 99%

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Effects of Gangliosides on Spermatozoa, Oocytes, and Preimplantation Embryos

Kim

et al. 2019

IJMS

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Gangliosides are sialic acid-containing glycosphingolipids, which are the most abundant family of glycolipids in eukaryotes. Gangliosides have been suggested to be important lipid molecules required for the control of cellular procedures, such as cell differentiation, proliferation, and signaling. GD1a is expressed in interstitial cells during ovarian maturation in mice and exogenous GD1a is important to oocyte maturation, monospermic fertilization, and embryonic development. In this context, GM1 is known to influence signaling pathways in cells and is important in sperm–oocyte interactions and sperm maturation processes, such as capacitation. GM3 is expressed in the vertebrate oocyte cytoplasm, and exogenously added GM3 induces apoptosis and DNA injury during in vitro oocyte maturation and embryogenesis. As a consequence of this, ganglioside GT1b and GM1 decrease DNA fragmentation and act as H2O2 inhibitors on germ cells and preimplantation embryos. This review describes the functional roles of gangliosides in spermatozoa, oocytes, and early embryonic development.

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Section: Gangliosides On Oocytes and Preimplantation Embryossupporting

confidence: 56%

Section: Gangliosides On Oocytes and Preimplantation Embryosmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of Gangliosides on Spermatozoa, Oocytes, and Preimplantation Embryos

Kim

et al. 2019

IJMS

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“…Thus, GSLs can modify cell signaling in response to specific stimuli. Examples for this are the interactions of GSLs with EGFR (Hofman et al, 2008;Park et al, 2017;Coskun et al, 2011) and the notch ligand delta-like 1 (Dll1) (Heuss et al, 2013). Here, their signalingand as a consequence, the downstream transcriptional responsesare influenced by their interaction with GSLs at the PM.…”

Section: The Regulatory Circuits Of Gsl Expressionmentioning

confidence: 99%

Glycosphingolipid metabolism in cell fate specification

Russo

Capolupo

Loomba

et al. 2018

Journal of Cell Science

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Glycosphingolipids (GSLs) are ubiquitous components of eukaryotic plasma membranes that consist of a ceramide backbone linked to a glycan moiety. Both the ceramide and the glycan parts of GSLs display structural variations that result in a remarkable repertoire of diverse compounds. This diversity of GSLs is exploited during embryogenesis, when different GSLs are produced at specific developmental stages and along several differentiation trajectories. Importantly, plasma membrane receptors interact with GSLs to modify their activities. Consequently, two otherwise identical cells can respond differently to the same stimulus owing to their different GSL composition. The metabolic reprograming of GSLs is in fact a necessary part of developmental programs, as its impairment results in developmental failure or tissue-specific defects. Moreover, single-cell variability is emerging as a fundamental player in development: GSL composition displays cell-to-cell variability in syngeneic cell populations owing to the regulatory gene expression circuits involved in microenvironment adaptation and in differentiation. Here, we discuss how GSLs are synthesized and classified and review the role of GSLs in the establishment and maintenance of cell identity. We further highlight the existence of the regulatory circuits that modify GSL pathways and speculate how GSL heterogeneity might contribute to developmental patterning.

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“…In a previous report, the PI3K/AKT signaling pathway was associated with the developmental competence of bovine oocytes [ 12 ]. Additionally, supplementation with certain proteins (e.g., hormones and gangliosides) in IVM medium affects the developmental capacity via modulation of the PI3K/AKT signaling pathway [ 13 , 14 ]. Therefore, it has been suggested that the AKT activity in oocytes differs between class I and class II COCs and that it might be regulated to increase maturation competence and subsequent early embryonic development.…”

Section: Introductionmentioning

confidence: 99%

The effects of kinase modulation on in vitro maturation according to different cumulus-oocyte complex morphologies

Song¹,

Jeong²,

Lee³

et al. 2018

PLoS ONE

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Successful production of transgenic pigs requires oocytes with a high developmental competence. However, cumulus–oocyte complexes (COCs) obtained from antral follicles have a heterogeneous morphology. COCs can be classified into one of two classes: class I, with five or more layers of cumulus cells; and class II, with one or two layers of cumulus cells. Activator [e.g., epidermal growth factor (EGF)] or inhibitors (e.g., wortmannin and U0126) are added to modulate kinases in oocytes during meiosis. In the present study, we investigated the effects of kinase modulation on nuclear and cytoplasmic maturation in COCs. Class I COCs showed a significantly higher developmental competence than class II COCs. Moreover, the expression of two kinases, AKT and ERK, differed between class I and class II COCs during in vitro maturation (IVM). Initially, inhibition of the PI3K/AKT signaling pathway in class I COCs during early IVM (0–22 h) decreased developmental parameters, such as blastocyst formation rate, blastomere number, and cell survival. Conversely, EGF-mediated AKT activation in class II COCs enhanced developmental capacity. Regarding the MAPK signaling pathway, inhibition of ERK by U0126 in class II COCs during early IVM impaired developmental competence. However, transient treatment with U0126 in class II COCs increased oocyte maturation and AKT activity, improving embryonic development. Additionally, western blotting showed that inhibition of ERK activity negatively regulated the AKT signaling pathway, indicative of a relationship between AKT and MAPK signaling in the process underlying meiotic progression in pigs. These findings may help increase the developmental competence and utilization rate of pig COCs with regard to the production of transgenic pigs and improve our understanding of kinase-associated meiosis events.

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Ganglioside GM3 induces cumulus cell apoptosis through inhibition of epidermal growth factor receptor‐mediated PI3K/AKT signaling pathways during in vitro maturation of pig oocytes

Cited by 23 publications

References 32 publications

Effects of Gangliosides on Spermatozoa, Oocytes, and Preimplantation Embryos

Effects of Gangliosides on Spermatozoa, Oocytes, and Preimplantation Embryos

Glycosphingolipid metabolism in cell fate specification

The effects of kinase modulation on in vitro maturation according to different cumulus-oocyte complex morphologies

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