Wei Yaozong, Pan Bo, Qin Jianpeng, Cao Beijia, Lv Tianyi, Ye Jiangfeng, Ning Ao, Du Kunlin, Chen Xiangyi, Zou Shuqi, Zang Shengqin, Yu Guozhi, Song Tianzeng, Liang Qiuxia, Zhou Guangbin
State Key Laboratory of Swine and Poultry Breeding Industry, Key Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, and Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, 611130, China.
College of Life Science, Sichuan Agricultural University, Ya'an, 625014, Sichuan, China.
J Anim Sci Biotechnol. 2024 Jun 11;15(1):86. doi: 10.1186/s40104-024-01045-0.
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.
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.
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.
先前的研究表明，中期II（MII）卵母细胞的玻璃化显著抑制其发育潜能。氧化应激异常增加可能是原因，但潜在机制仍不清楚。核桃衍生肽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潜在应用尚未见报道。
在这里，我们发现来自玻璃化MII卵母细胞的孤雌激活（PA）合子显示出升高的活性氧水平和原核形成进程延迟。在解冻、复苏、PA和胚胎培养基中添加25μmol/L TW-7可以减轻玻璃化小鼠MII卵母细胞PA合子中的氧化应激，进一步增加与组蛋白乳酸化相关的蛋白质，如LDHA、LDHB和EP300，最终改善PA合子中的组蛋白乳酸化。升高的组蛋白乳酸化促进了微小合子基因组激活（ZGA）基因的表达和植入前胚胎发育。
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，可显著挽救玻璃化卵母细胞降低的发育潜能，这可能对生殖医学、动物保护和育种有帮助。
