The walnut-derived peptide TW-7 improves mouse parthenogenetic embryo development of vitrified MII oocytes potentially by promoting histone lactylation.
Yaozong Wei, Bo Pan, Jianpeng Qin, Beijia Cao, Tianyi Lv, Jiangfeng Ye, Ao Ning, Kunlin Du, Xiangyi Chen, Shuqi Zou, Shengqin Zang, Guozhi Yu, Tianzeng Song, Qiuxia Liang, Guangbin Zhou
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引用次数: 0
Abstract
Background: Previous studies have shown that the vitrification of metaphase II (MII) oocytes significantly represses their developmental potential. Abnormally increased oxidative stress is the probable factor; however, the underlying mechanism remains unclear. The walnut-derived peptide TW-7 was initially isolated and purified from walnut protein hydrolysate. Accumulating evidences implied that TW-7 was a powerful antioxidant, while its prospective application in oocyte cryopreservation has not been reported.
Result: Here, we found that parthenogenetic activation (PA) zygotes derived from vitrified MII oocytes showed elevated ROS level and delayed progression of pronucleus formation. Addition of 25 μmol/L TW-7 in warming, recovery, PA, and embryo culture medium could alleviate oxidative stress in PA zygotes from vitrified mouse MII oocytes, furtherly increase proteins related to histone lactylation such as LDHA, LDHB, and EP300 and finally improve histone lactylation in PA zygotes. The elevated histone lactylation facilitated the expression of minor zygotic genome activation (ZGA) genes and preimplantation embryo development.
Conclusions: Our findings revealed the mechanism of oxidative stress inducing repressed development of PA embryos from vitrified mouse MII oocytes and found a potent and easy-obtained short peptide that could significantly rescue the decreased developmental potential of vitrified oocytes, which would potentially contribute to reproductive medicine, animal protection, and breeding.
背景:先前的研究表明,玻璃化的 II 期卵母细胞(MII)会显著抑制其发育潜能。氧化应激异常增加是可能的因素,但其潜在机制仍不清楚。核桃肽 TW-7 最初是从核桃蛋白水解物中分离和纯化出来的。越来越多的证据表明 TW-7 是一种强大的抗氧化剂,但其在卵母细胞冷冻保存中的应用前景尚未见报道:结果:在这里,我们发现从玻璃化的 MII 卵母细胞中获得的孤雌生殖激活(PA)子代表现出 ROS 水平升高和前核形成进展延迟。在温育、复苏、PA和胚胎培养液中添加25 μmol/L TW-7可缓解玻璃化小鼠MII卵母细胞产生的PA子代的氧化应激,进一步增加与组蛋白乳化相关的蛋白质,如LDHA、LDHB和EP300,最终改善PA子代的组蛋白乳化。组蛋白乳化的提高促进了次要子代基因组激活(ZGA)基因的表达和植入前胚胎的发育:我们的研究结果揭示了氧化应激诱导玻璃化小鼠 MII 卵母细胞 PA 胚胎发育受抑制的机制,并发现了一种有效且易于获得的短肽,它能显著挽救玻璃化卵母细胞发育潜能的下降,这将为生殖医学、动物保护和育种做出潜在贡献。