The 23rd International Symposium on Developmental Biotechnology[Hun-Wook Ha] > 학회발표

Ochratoxin A Impairs Embryonic Development by Inhibiting SEC62-Mediated ER-Phagy Through ATF5-Dependent UPR Activation

Hun-Wook Ha^1,2*, Hyo-Jin Park^{1, 2} , Ye-Won Jang^2,3, Su-Hyun Han^2,3 and Deog-Bon Koo^{1, 2, 3**}

¹Department of Biotechnology, College of Engineering, ²Center for Infertility, ³Department of Companion Animal Industry, College of Natural and Life Sciences, Daegu University, 201 Daegudae-ro Jillyang, Gyeongsan, Gyeongbuk 38453, Republic of Korea

Ochratoxin A (OTA), a mycotoxin frequently detected in cereal-based feeds, impairs porcine embryonic development during in vitro culture (IVC) by inducing oxidative and endoplasmic reticulum (ER) stress. However, the detailed mechanisms by which OTA-mediated ER stress affects selective autophagy remain unclear. Tunicamycin (Tm), a well-known ER stress inducer, was used as a positive control to compare OTA-induced responses. Porcine embryos were cultured in IVC medium supplemented with 0.5 µM OTA or 1 µg/mL Tm for 2 days. As expected, OTA treatment significantly reduced (p < 0.05) the blastocyst formation rate and total cell number, accompanied by an increase in apoptotic nuclei and reactive oxygen species (ROS) accumulation. Both OTA- and Tm-treated embryos exhibited abnormal perinuclear aggregation of the ER, indicating persistent ER stress. Western blot analysis revealed that OTA exposure markedly increased the expression of BiP, p-PERK, p-eIF2α, and ATF5, confirming activation of the PERK–eIF2α–ATF5 pathway. Importantly, SEC62 a key ER-phagy receptor acts as an intersectional regulator linking the ATF5-mediated UPR signaling pathway to ER-phagy. OTA exposure significantly decreased SEC62 expression, suggesting that disruption of SEC62 may uncouple ATF5-driven UPR signaling from ER-phagy regulation. In addition, the autophagy marker LC3B-II was significantly increased, whereas another ER-phagy receptor protein, FAM134B, was also downregulated. These findings indicate that OTA activates PERK–ATF5 signaling and enhances general autophagosome accumulation while suppressing receptor-mediated ER-phagy through downregulation of SEC62 and FAM134B.

Consequently, the impairment of SEC62-mediated crosstalk between the UPR and ER-phagy pathways leads to blockage of ER-phagy flux, disruption of ER homeostasis, and ultimately reduced embryonic developmental competence.

Keywords: Ochratoxin A(OTA), Endoplasmic reticulum (ER)-stress, SEC62, ER-phagy, Porcine embryos

E-mail: gjsdnr991129@naver.com (Hun-Wook Ha)

Funding

This work was supported by the National Research Foundation of Korea (NRF) funded by the government (MSIT) of the Republic of Korea (RS-2021-NR061941 and RS-2022-NR069006). This study was supported by the Gyeongsangbuk-do Regional Innovation System and Education (RISE) Project.