(55) Zearalenone-Induced Endoplasmic Reticulum Stress Modulates IRE1-Mediated ER-Phagy Activation in Preimplantation Porcine Embryos

Zearalenone-Induced Endoplasmic Reticulum Stress Modulates IRE1-Mediated ER-Phagy Activation in Preimplantation Porcine Embryos

Hyo-Jin Park^1,2, Dong-Woo Kim^1,2, Seul-Gi Yang^2,3, Eun-Seo Kim^1,2, Hun-Wook Ha^1,2, Geun-Hwi Jo^1,2, and Deog-Bon Koo^1,2,3

1. Department of Biotechnology, Daegu University, 201 Daegudae-ro, Jillyang, Gyeongsan, Gyeongbuk 38453, Republic of Korea

2. DU Center for Infertility, Daegu University, 201 Daegudae-ro, Jillyang, Gyeongsan, Gyeongbuk 38453, Republic of Korea

3. Department of Companion Animal Industry, Daegu University, 201 Daegudae-ro, Jillyang, Gyeongsan 38453, Republic of Korea

Abstract Text:

The purpose of the present study was to investigate the molecular mechanisms of inositol-requiring enzyme 1 (IRE1) signaling and family with sequence similarity 134 member B (FAM134B)-mediated endoplasmic reticulum (ER) phagy in embryonic developmental competence under zearalenone (ZEA)-induced ER stress in porcine embryos during in vitro culture. Porcine embryos were cultured in IVC medium with 2.5, 5, and 10 μM ZEN for 2 days to assess blastocyst development competence. ZEA-induced uneven ER distribution and increased Ca²⁺ levels in mitochondria impaired embryonic development in a dose-dependent manner. This study examined whether ZEN induces ER stress-related autophagy through IRE1 signaling in porcine embryos by analyzing the co-expression of LC3B, FAM134B, and ER-Tracker. We confirmed a significant increase in the protein levels of IRE1 pathway components (GRP78, p-IRE1, and IRE1) and the autophagy marker LC3B in ZEN-treated porcine embryos (p < 0.05) by using Western blot analysis. Conversely, the protein level of the ER-phagy receptor FAM134B was significantly decreased in ZEN-treated porcine blastocysts. Tauroursodeoxycholic acid, an ER stress inhibitor, enhances blastocyst development by mitigating oxidative stress, ER distribution abnormalities, autophagy, and FAM134B-derived ER-phagy in ZEN-exposed porcine embryos. In conclusion, this study provides evidence that ZEN-exposed porcine embryos inhibit IRE1-mediated ER-phagy, leading to increased ER stress and apoptosis, ultimately impairing embryonic developmental capacity.

Funding

This research was supported by the National Research Foundation of Korea (NRF) funded by the Korea government (MSIT) (NRF-2021R1C1C2009469 and NRF-2022R1A2C1002800) and the Basic Science Research Program through the NRF funded by the Ministry of Education (RS-2023-00246139), Republic of Korea.