2023년 한국동물생명공학회 학술 대회 [Hyo-Jin Park] > 학회발표

Roles on PERK/SESN2/NRF2 signaling pathways response to ER-stress in porcine embryos preimplantation 

Hyo-Jin Park^1,2 

 ¹Department of Biotechnology, College of Engineering, Daegu University, 201 Daegudae-ro, Jillyang, Gyeongsan, Gyeongbuk 38453, Republic of Korea, ² Institute of Infertility, Daegu University, 201 Daegudae-ro, Jillyang, Gyeongsan, Gyeongbuk 38453, Republic of Korea

 Nuclear erythroid 2-related factor 2 (NRF2) is a critical regulator of oxidative stress in mammalian oocytes. Our previous study described the protective effects of Sestrin-2 (SESN2) as a stress regulator against endoplasmic reticulum (ER) stress in porcine oocytes during in vitro maturation (IVM). However, their roles in unfolded protein response-related signaling pathways in porcine oocyte maturation capacity remain unknown. The purpose of this study was to evaluate the role of SESN2/NRF2 signaling in H2O2-induced oxidative stress and ER stress via protein kinase-like ER kinase (PERK) downstream factor during porcine oocyte maturation. Here, we found that the p-NRF2(Ser40) activation in the nucleus of porcine oocytes was accompanied by PERK signaling downregulation using Western blot and immunofluorescence staining at 44 h after IVM. The total and nuclear NRF2 protein expressions were also induced in porcine oocytes following H2O2 and tunicamycin (Tm) exposure. Notably, the upregulation of PERK signaling significantly increased the SESN2 and NRF2 signaling in H2O2-and Tm-exposed porcine cumulus-oocyte complexes. Interestingly, inducing the knockdown of the SESN2 gene expression by siRNA interrupted the NRF2 signaling activation of porcine oocyte maturation, whereas NRF2 expression blockade by ochratoxin A, an NRF2 inhibitor, did not affect the expression level of the SESN2 protein. Moreover, a defect in SESN2 completely blocked the activity of nuclear NRF2 on spindle assembly in porcine oocytes. These findings suggest that the PERK/SESN2/NRF2 signaling pathway may play an important role against ER stress during meiotic maturation and oocyte maturation capacity. 

*This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF-2021R1C1C2009469, NRF-2022R1A2C1002800, and NRF-2021R1A6A3A01087623) funded by and the Ministry of Science and ICT, Republic of Korea.

KEYWORDS 

Endoplasmic reticulum stress (ER stress), protein kinase-like ER kinase (PERK) signal, (Nuclear erythroid 2-related factor 2) NRF2, Sestrin-2 (SESN2), oocyte maturation