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Regulation of the Endoplasmic Reticulum Stress by BIP/GRP78 is involved in Meiotic Maturation of Porcine Oocytes In Vitro

  • Park, Hyo-Jin (Dept. of Biotechnology, College of Engineering, Daegu University) ;
  • Park, Jae-Young (Dept. of Biotechnology, College of Engineering, Daegu University) ;
  • Kim, Jin-Woo (Dept. of Biotechnology, College of Engineering, Daegu University) ;
  • Yang, Seul-Gi (Dept. of Biotechnology, College of Engineering, Daegu University) ;
  • Jung, Jae-Min (Dept. of Biotechnology, College of Engineering, Daegu University) ;
  • Kim, Min-Ji (Dept. of Biotechnology, College of Engineering, Daegu University) ;
  • Park, Joung Jun (Animal Reproduction & Biotechnology Center, Myung-Poom Hanwoo Consulting) ;
  • Koo, Deog-Bon (Dept. of Biotechnology, College of Engineering, Daegu University)
  • Received : 2017.10.15
  • Accepted : 2017.12.04
  • Published : 2017.12.31

Abstract

In the present study, we investigated the role of binding immunoglobulin protein/glucose-regulated protein, 78-kDa (BIP/GRP78)-regulated endoplasmic reticulum (ER)-stress on meiotic maturation and cumulus cells expansion in porcine cumulus-oocyte complexes (COCs). Previously, it has been demonstrated that unfolded protein response (UPR)-related genes, such as molecules involved in ER-stress defense mechanisms, were expressed in matured oocytes and cumulus cells during in vitro maturation (IVM) of porcine oocytes. However, BIP/GRP78-mediated regulation of ER stress in porcine oocytes has not been reported. Firstly, we observed the effects of knockdown of BIP/GRP78 (an UPR initiation marker) using porcine-specific siRNAs (#909, #693, and #1570) on oocyte maturation. Among all siRNAs, siRNA #693 significantly reduced the protein levels of UPR marker proteins (BIP/GRP78, ATF4, and P90ATF6) in porcine COCs observed by Western blotting and immunofluorescence analysis. We also observed that the reduction of BIP/GRP78 levels by siRNA#693 significantly inhibited the meiotic maturation of oocytes (siRNA #693: $32.5{\pm}10.1%$ vs control: $77.8{\pm}5.3%$). In addition, we also checked the effect of ER-stress inhibitors, tauroursodeoxycholic acid (TUDCA, $200{\mu}M$) and melatonin ($0.1{\mu}M$), in BIP/GRP78-knockdown oocytes. TUDCA and melatonin treatment could restore the expression levels of ER-stress marker proteins (BIP/GRP78, $p-eIF2{\alpha}$, $eIF2{\alpha}$, ATF4, and P90ATF6) in siRNA #693-transfected matured COCs. In conclusion, these results demonstrated that BIP/GRP78-mediated regulation of UPR signaling and ER stress plays an important role in in vitro maturation of porcine oocytes.

Keywords

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