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矢车菊素-3-O-葡萄糖苷通过减轻 NOX4 依赖性氧化应激和卵丘细胞内质网应激来保护 Zearalenone 诱导的猪卵母细胞体外成熟障碍。

Cyanidin-3-O-glucoside protects Zearalenone-induced in vitro maturation disorders of porcine oocytes by alleviating NOX4-dependent oxidative stress and endoplasmic reticulum stress in cumulus cells.

机构信息

College of Life Sciences, Key Laboratory of Animal Reproduction and Biotechnology in Universities of Shandong, Qingdao Agricultural University, Qingdao, 266109, China; College of Fisheries, Henan Normal University, Xinxiang, 453007, China; College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, 271018, China.

College of Life Sciences, Key Laboratory of Animal Reproduction and Biotechnology in Universities of Shandong, Qingdao Agricultural University, Qingdao, 266109, China; State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock (R2BGL), College of Life Sciences, Inner Mongolia University, Hohhot, 010070, China.

出版信息

Chemosphere. 2024 Jun;358:142153. doi: 10.1016/j.chemosphere.2024.142153. Epub 2024 Apr 28.

DOI:10.1016/j.chemosphere.2024.142153
PMID:38688352
Abstract

Zearalenone (ZEN) is widely found in foodstuffs and has serious harmful effects on female fertility, especially in pigs. Cyanidin-3-O-glucoside (C3G), a type of anthocyanin, exists in most dark fruits and vegetables; it has many positive dietary effects including as an antioxidant, anti-inflammatory, or anti-apoptotic agent. However, the beneficial effects of C3G alongside ZEN-induced damage in porcine oocytes and the underlying molecular mechanism have not been investigated. In this work, porcine cumulus-oocyte complexes (COCs) were divided into Control (Ctrl), ZEN, ZEN + C3G (Z + C), and C3G, and treated for 44-46 h in vitro. The results showed that C3G could alleviate ZEN-induced disorders of first polar body (PBI) extrusion, abnormalities of spindle assembly, cortical granule distribution, and mitochondrial distribution; these results were produced via restoring transzonal projections (TZPs), and inhibiting nicotinamide adenine dinucleotide phosphate oxidase (NOX4)-dependent oxidative stress and 'glucose regulatory protein 78/protein kinase-like endoplasmic reticulum kinase/α subunit of eukaryotic initiation factor 2α/activating transcription factor 4/C/EBP-homologous protein' (GRP78/PERK/eIF2α/ATF4/CHOP)-mediated endoplasmic reticulum stress (ERS) during oocyte maturation. Moreover, the over-expression of NOX4 in cumulus cells could result in a significant increase in ROS levels and ER fluorescence intensity in oocytes. In conclusion, C3G promoted in vitro maturation of porcine oocytes exposed to ZEN via mitigating NOX4-dependent oxidative stress and ERS in cumulus cells. These results contribute to our comprehension of the molecular mechanisms underlying the protective effects of C3G against ZEN toxicity in porcine oocytes, and they provide a novel theoretical foundation and strategy for future applications of C3G in the improvement of female reproduction.

摘要

玉米赤霉烯酮(ZEN)广泛存在于食品中,对雌性生育力有严重的有害影响,特别是在猪中。矢车菊素-3-O-葡萄糖苷(C3G)是一种花色苷,存在于大多数深色水果和蔬菜中;它具有许多积极的饮食作用,包括抗氧化剂、抗炎剂或抗凋亡剂。然而,C3G 与 ZEN 诱导的猪卵母细胞损伤以及潜在的分子机制之间的有益相互作用尚未得到研究。在这项工作中,猪卵丘-卵母细胞复合物(COCs)分为对照组(Ctrl)、ZEN 组、ZEN+C3G 组(Z+C)和 C3G 组,并在体外培养 44-46 小时。结果表明,C3G 可减轻 ZEN 诱导的第一极体(PBI)排出障碍、纺锤体组装异常、皮质颗粒分布和线粒体分布;这些结果是通过恢复透明带突起(TZPs),抑制烟酰胺腺嘌呤二核苷酸磷酸氧化酶(NOX4)依赖性氧化应激和“葡萄糖调节蛋白 78/蛋白激酶样内质网激酶/真核起始因子 2α 的α亚基/激活转录因子 4/C/EBP 同源蛋白”(GRP78/PERK/eIF2α/ATF4/CHOP)介导的内质网应激(ERS)而产生的在卵母细胞成熟过程中。此外,在卵丘细胞中过表达 NOX4 可导致卵母细胞中 ROS 水平和 ER 荧光强度显著增加。总之,C3G 通过减轻 cumulus 细胞中 NOX4 依赖性氧化应激和 ERS,促进了暴露于 ZEN 的猪卵母细胞的体外成熟。这些结果有助于我们理解 C3G 对猪卵母细胞中 ZEN 毒性的保护作用的分子机制,并为 C3G 在改善女性生殖力方面的未来应用提供了新的理论基础和策略。

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