Lysophosphatidic acid increases in vitro maturation efficiency via uPA-uPAR signaling pathway in cumulus cells

Seon Ung Hwang; Kyu Jun Kim; Eunhye Kim; Junchul David Yoon; Kyu Mi Park; Minghui Jin; Yongquan Han; Mirae Kim; Gabsang Lee; Sang Hwan Hyun

doi:10.1016/j.theriogenology.2018.02.020

Lysophosphatidic acid increases in vitro maturation efficiency via uPA-uPAR signaling pathway in cumulus cells

Seon Ung Hwang, Kyu Jun Kim, Eunhye Kim, Junchul David Yoon, Kyu Mi Park, Minghui Jin, Yongquan Han, Mirae Kim, Gabsang Lee, Sang Hwan Hyun

School of Medicine

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Lysophosphatidic acid (LPA) is a phospholipid-derived signaling molecule with biological activities, such as stimulating cell proliferation, differentiation and migration. In the present study, we examined the effect of LPA on porcine oocytes during in vitro maturation (IVM) and subsequent embryonic development following parthenogenetic activation (PA) and in vitro fertilization (IVF). During IVM, the maturation medium was supplemented with various concentrations of LPA (0, 10, 30, and 60 μM). After 42 h of IVM, the 30 μM LPA-treated group showed a significant (P < 0.05) increase in nuclear maturation and intracellular glutathione (GSH) levels compared with the other groups. The 30 μM LPA-treated group exhibited a significant decrease in intracellular reactive oxygen species (ROS) levels compared with the other groups. In PA, the 30 μM LPA-treated group had significantly higher cleavage (CL) and blastocyst (BL) rates compared with those of the other LPA-treated groups. In IVF, the 30 μM LPA-treated group had significantly higher CL and BL rates than the other LPA-treated groups. The expression of the developmental competence gene (proliferating cell nuclear antigen, PCNA) in the oocytes and cumulus cells of the individuals in the 30 μM LPA-treated group was significantly increased compared with the control group. In addition, the specific expression of urokinase Plasminogen Activator (uPA) and uPA Receptor (uPAR) in cumulus cells was significantly increased in the 30 μM LPA-treated group. The western blotting results revealed that LPA improves the activities of p38 mitogen-activated protein kinase (MAPK) and epidermal growth factor (EGF) by enhanced phosphorylation. In conclusion, treatment with 30 μM LPA during IVM promotes enhances the EGF-EGFR signaling pathway, resulting in cumulus cell expansion. And then, this treatment improves the developmental potential of PA and IVF porcine embryos by enhancing nuclear and cytoplasmic maturation and reducing ROS.

Original language	English (US)
Pages (from-to)	197-207
Number of pages	11
Journal	Theriogenology
Volume	113
DOIs	https://doi.org/10.1016/j.theriogenology.2018.02.020
State	Published - Jun 2018

Keywords

Cumulus cell
In vitro maturation
Lipid
Oocyte

ASJC Scopus subject areas

Small Animals
Food Animals
Animal Science and Zoology
Equine

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10.1016/j.theriogenology.2018.02.020

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@article{b73184f55e2646c0ae6ea056a78dc3c5,

title = "Lysophosphatidic acid increases in vitro maturation efficiency via uPA-uPAR signaling pathway in cumulus cells",

abstract = "Lysophosphatidic acid (LPA) is a phospholipid-derived signaling molecule with biological activities, such as stimulating cell proliferation, differentiation and migration. In the present study, we examined the effect of LPA on porcine oocytes during in vitro maturation (IVM) and subsequent embryonic development following parthenogenetic activation (PA) and in vitro fertilization (IVF). During IVM, the maturation medium was supplemented with various concentrations of LPA (0, 10, 30, and 60 μM). After 42 h of IVM, the 30 μM LPA-treated group showed a significant (P < 0.05) increase in nuclear maturation and intracellular glutathione (GSH) levels compared with the other groups. The 30 μM LPA-treated group exhibited a significant decrease in intracellular reactive oxygen species (ROS) levels compared with the other groups. In PA, the 30 μM LPA-treated group had significantly higher cleavage (CL) and blastocyst (BL) rates compared with those of the other LPA-treated groups. In IVF, the 30 μM LPA-treated group had significantly higher CL and BL rates than the other LPA-treated groups. The expression of the developmental competence gene (proliferating cell nuclear antigen, PCNA) in the oocytes and cumulus cells of the individuals in the 30 μM LPA-treated group was significantly increased compared with the control group. In addition, the specific expression of urokinase Plasminogen Activator (uPA) and uPA Receptor (uPAR) in cumulus cells was significantly increased in the 30 μM LPA-treated group. The western blotting results revealed that LPA improves the activities of p38 mitogen-activated protein kinase (MAPK) and epidermal growth factor (EGF) by enhanced phosphorylation. In conclusion, treatment with 30 μM LPA during IVM promotes enhances the EGF-EGFR signaling pathway, resulting in cumulus cell expansion. And then, this treatment improves the developmental potential of PA and IVF porcine embryos by enhancing nuclear and cytoplasmic maturation and reducing ROS.",

keywords = "Cumulus cell, In vitro maturation, Lipid, Oocyte",

author = "Hwang, {Seon Ung} and Kim, {Kyu Jun} and Eunhye Kim and Yoon, {Junchul David} and Park, {Kyu Mi} and Minghui Jin and Yongquan Han and Mirae Kim and Gabsang Lee and Hyun, {Sang Hwan}",

note = "Funding Information: This work was supported, in part, by a grant from the “ National Research Foundation of Korea Grant funded by the Korean Government ( NRF-2016R1D1A1B03933191 , NRF-2017R1A2B4002546 )“, “The Global Research and Development Center (GRDC) Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2017K1A4A3014959 )” and “ Business for Cooperative R&D between Industry, Academy, and Research Institute funded Korea Small and Medium Business Administration in 2017 (Grants No. 2017020681010101 )”, Republic of Korea. Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",

year = "2018",

month = jun,

doi = "10.1016/j.theriogenology.2018.02.020",

language = "English (US)",

volume = "113",

pages = "197--207",

journal = "Theriogenology",

issn = "0093-691X",

publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Lysophosphatidic acid increases in vitro maturation efficiency via uPA-uPAR signaling pathway in cumulus cells

AU - Hwang, Seon Ung

AU - Kim, Kyu Jun

AU - Kim, Eunhye

AU - Yoon, Junchul David

AU - Park, Kyu Mi

AU - Jin, Minghui

AU - Han, Yongquan

AU - Kim, Mirae

AU - Lee, Gabsang

AU - Hyun, Sang Hwan

N1 - Funding Information: This work was supported, in part, by a grant from the “ National Research Foundation of Korea Grant funded by the Korean Government ( NRF-2016R1D1A1B03933191 , NRF-2017R1A2B4002546 )“, “The Global Research and Development Center (GRDC) Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2017K1A4A3014959 )” and “ Business for Cooperative R&D between Industry, Academy, and Research Institute funded Korea Small and Medium Business Administration in 2017 (Grants No. 2017020681010101 )”, Republic of Korea. Publisher Copyright: © 2018 Elsevier Inc.

PY - 2018/6

Y1 - 2018/6

N2 - Lysophosphatidic acid (LPA) is a phospholipid-derived signaling molecule with biological activities, such as stimulating cell proliferation, differentiation and migration. In the present study, we examined the effect of LPA on porcine oocytes during in vitro maturation (IVM) and subsequent embryonic development following parthenogenetic activation (PA) and in vitro fertilization (IVF). During IVM, the maturation medium was supplemented with various concentrations of LPA (0, 10, 30, and 60 μM). After 42 h of IVM, the 30 μM LPA-treated group showed a significant (P < 0.05) increase in nuclear maturation and intracellular glutathione (GSH) levels compared with the other groups. The 30 μM LPA-treated group exhibited a significant decrease in intracellular reactive oxygen species (ROS) levels compared with the other groups. In PA, the 30 μM LPA-treated group had significantly higher cleavage (CL) and blastocyst (BL) rates compared with those of the other LPA-treated groups. In IVF, the 30 μM LPA-treated group had significantly higher CL and BL rates than the other LPA-treated groups. The expression of the developmental competence gene (proliferating cell nuclear antigen, PCNA) in the oocytes and cumulus cells of the individuals in the 30 μM LPA-treated group was significantly increased compared with the control group. In addition, the specific expression of urokinase Plasminogen Activator (uPA) and uPA Receptor (uPAR) in cumulus cells was significantly increased in the 30 μM LPA-treated group. The western blotting results revealed that LPA improves the activities of p38 mitogen-activated protein kinase (MAPK) and epidermal growth factor (EGF) by enhanced phosphorylation. In conclusion, treatment with 30 μM LPA during IVM promotes enhances the EGF-EGFR signaling pathway, resulting in cumulus cell expansion. And then, this treatment improves the developmental potential of PA and IVF porcine embryos by enhancing nuclear and cytoplasmic maturation and reducing ROS.

AB - Lysophosphatidic acid (LPA) is a phospholipid-derived signaling molecule with biological activities, such as stimulating cell proliferation, differentiation and migration. In the present study, we examined the effect of LPA on porcine oocytes during in vitro maturation (IVM) and subsequent embryonic development following parthenogenetic activation (PA) and in vitro fertilization (IVF). During IVM, the maturation medium was supplemented with various concentrations of LPA (0, 10, 30, and 60 μM). After 42 h of IVM, the 30 μM LPA-treated group showed a significant (P < 0.05) increase in nuclear maturation and intracellular glutathione (GSH) levels compared with the other groups. The 30 μM LPA-treated group exhibited a significant decrease in intracellular reactive oxygen species (ROS) levels compared with the other groups. In PA, the 30 μM LPA-treated group had significantly higher cleavage (CL) and blastocyst (BL) rates compared with those of the other LPA-treated groups. In IVF, the 30 μM LPA-treated group had significantly higher CL and BL rates than the other LPA-treated groups. The expression of the developmental competence gene (proliferating cell nuclear antigen, PCNA) in the oocytes and cumulus cells of the individuals in the 30 μM LPA-treated group was significantly increased compared with the control group. In addition, the specific expression of urokinase Plasminogen Activator (uPA) and uPA Receptor (uPAR) in cumulus cells was significantly increased in the 30 μM LPA-treated group. The western blotting results revealed that LPA improves the activities of p38 mitogen-activated protein kinase (MAPK) and epidermal growth factor (EGF) by enhanced phosphorylation. In conclusion, treatment with 30 μM LPA during IVM promotes enhances the EGF-EGFR signaling pathway, resulting in cumulus cell expansion. And then, this treatment improves the developmental potential of PA and IVF porcine embryos by enhancing nuclear and cytoplasmic maturation and reducing ROS.

KW - Cumulus cell

KW - In vitro maturation

KW - Lipid

KW - Oocyte

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U2 - 10.1016/j.theriogenology.2018.02.020

DO - 10.1016/j.theriogenology.2018.02.020

M3 - Article

C2 - 29554602

AN - SCOPUS:85043978386

SN - 0093-691X

VL - 113

SP - 197

EP - 207

JO - Theriogenology

JF - Theriogenology

ER -

Lysophosphatidic acid increases in vitro maturation efficiency via uPA-uPAR signaling pathway in cumulus cells

Abstract

Keywords

ASJC Scopus subject areas

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