Department of Biotechnology, Daegu University, 201 Daegudae-ro, Jillyang, Gyeongsan, Gyeongbuk, 38453, Republic of Korea; DU Center for Infertility, Daegu University, 201 Daegudae-ro, Jillyang, Gyeongsan, Gyeongbuk, 38453, Republic of Korea.
DU Center for Infertility, Daegu University, 201 Daegudae-ro, Jillyang, Gyeongsan, Gyeongbuk, 38453, Republic of Korea; Department of Companion Animal Industry, Daegu University, 201 Daegudae-ro, Jillyang, Gyeongsan, 38453, Republic of Korea.
Food Chem Toxicol. 2024 Jun;188:114633. doi: 10.1016/j.fct.2024.114633. Epub 2024 Apr 10.
The cytotoxic mycotoxin deoxynivalenol (DON) reportedly has adverse effects on oocyte maturation and embryonic development in pigs. Recently, the interplay between cell apoptosis and endoplasmic reticulum (ER) stress has garnered increasing attention in embryogenesis. However, the involvement of the inositol-requiring enzyme 1 (IRE1)/c-jun N-terminal kinase (JNK)/C/EBP homologous protein (CHOP) pathways of unfolded protein response (UPR) signaling in DON-induced apoptosis in porcine embryos remains unknown. In this study, we revealed that exposure to DON (0.25 μM) substantially decreased cell viability until the blastocyst stage in porcine embryos, concomitant with initiation of cell apoptosis through the IRE1/JNK/CHOP pathways in response to ER stress. Quantitative PCR confirmed that UPR signaling-related transcription factors were upregulated in DON-treated porcine blastocysts. Western blot analysis showed that IRE1/JNK/CHOP signaling was activated in DON-exposed porcine embryos, indicating that ER stress-associated apoptosis was instigated. The ER stress inhibitor tauroursodeoxycholic acid protected against DON-induced ER stress in porcine embryos, indicating that the toxic effects of DON on early developmental competence of porcine embryos can be prevented. In conclusion, DON exposure impairs the developmental ability of porcine embryos by inducing ER stress-mediated apoptosis via IRE1/JNK/CHOP signaling.
据报道，细胞毒性真菌毒素脱氧雪腐镰刀菌烯醇（DON）对猪卵母细胞成熟和胚胎发育有不良影响。最近，细胞凋亡与内质网（ER）应激之间的相互作用在胚胎发生中受到越来越多的关注。然而，未折叠蛋白反应（UPR）信号通路中的肌醇需求酶 1（IRE1）/c-jun N 末端激酶（JNK）/C/EBP 同源蛋白（CHOP）途径在 DON 诱导猪胚胎细胞凋亡中的参与尚不清楚。在这项研究中，我们揭示了 DON（0.25 μM）暴露会显著降低猪胚胎的细胞活力，直到囊胚阶段，同时通过 IRE1/JNK/CHOP 途径响应 ER 应激引发细胞凋亡。定量 PCR 证实了 UP R 信号相关转录因子在 DON 处理的猪囊胚中上调。Western blot 分析表明，IRE1/JNK/CHOP 信号在 DON 暴露的猪胚胎中被激活，表明 ER 应激相关的细胞凋亡被引发。ER 应激抑制剂牛磺熊脱氧胆酸可防止 DON 诱导的猪胚胎 ER 应激，表明 DON 对猪胚胎早期发育能力的毒性作用可以得到预防。总之，DON 暴露通过 IRE1/JNK/CHOP 信号诱导 ER 应激介导的凋亡，损害猪胚胎的发育能力。
