Melatonin improves the meiotic maturation of porcine oocytes by reducing endoplasmic reticulum stress during in vitro maturation

Journal of Pineal Research - Tập 64 Số 2 - 2018
Hyo‐Jin Park1, Jae‐Young Park1,2, Jin‐Woo Kim1, Seul‐Gi Yang1, Jaemin Jung1, Min‐Ji Kim1, Man‐Jong Kang3, Young Ho Cho4, Gabbine Wee5, Heeyoung Yang5, Bong‐Seok Song6, Sun‐Uk Kim6, Deog‐Bon Koo1
1Department of Biotechnology, College of Engineering, Daegu University, Jillyang, Gyeongsan, Gyeongbuk, Korea
2Saewha Hospital, Dongnae, Busan, Korea
3Department of Animal Science, College of Agriculture and Life Sciences, Chonnam National University, Gwangju, Korea
4Department of Pharmaceutics & Biotechnology, College of Medical Engineering, Konyang University, Daejeon, Korea
5Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu, Korea
6National Primate Research Center & Futuristic Animal Resource and Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungbuk, Korea

Tóm tắt

AbstractUnder endoplasmic reticulum (ER)‐stress conditions, the unfolded protein response (UPR) generates a defense mechanism in mammalian cells. The regulation of UPR signaling is important in oocyte maturation, embryo development, and female reproduction of pigs. Recent studies have shown that melatonin plays an important role as an antioxidant to improve pig oocyte maturation. However, there is no report on the role of melatonin in the regulation of UPR signaling and ER‐stress during in vitro maturation (IVM) of porcine oocytes. Therefore, the objective of this study was to investigate the antioxidative effects of melatonin on porcine oocyte maturation through the regulation of ER‐stress and UPR signaling. We investigated the changes in the mRNA/protein expression levels of three UPR signal genes (Bip/Grp78, ATF4, P90/50ATF6, sXbp1, and CHOP) on oocytes, cumulus cells, and cumulus‐oocyte complexes (COCs) during IVM (metaphase I; 22 hours and metaphase II; 44 hours) by Western blot and reverse transcription‐polymerase chain reaction analysis. Treatment with the ER‐stress inducer, tunicamycin (Tm), significantly increased expression of UPR markers. Additionally, cumulus cell expansion and meiotic maturation of oocytes were reduced in COCs of Tm‐treated groups (1, 5, and 10 μg/mL). We confirmed the reducing effects of melatonin (0.1 μmol/L) on ER‐stress after pretreatment with Tm (5 μg/mL; 22 hours) in maturing COCs. Addition of melatonin (0.1 μmol/L) to Tm‐pretreated COCs recovered meiotic maturation rates and expression of most UPR markers. In conclusion, we confirmed a role for melatonin in the modulation of UPR signal pathways and reducing ER‐stress during IVM of porcine oocytes.

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