Jia Ruru, Lu Canqiang, Xia Fan, Wang Yanxin, Zhou Dongping, Liang Shiying, Wang Yun, Huang Xiaoqian, Chen Yanyu, Shi Deshun, Lu Fenghua
State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, Guangxi University, Nanning, 530005, China.
State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, Guangxi University, Nanning, 530005, China; Research Center for Environment and Female Reproductive Health, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518033, China.
Theriogenology. 2025 Oct 15;246:117555. doi: 10.1016/j.theriogenology.2025.117555. Epub 2025 Jun 25.
Lipogenic and catabolic processes constitute fundamental metabolic pathways that govern energy homeostasis during oocyte maturation and subsequent embryonic development. Although emerging evidence has highlighted the regulatory potential of Procyanidin B2 (PB2) in modulating meiotic progression and developmental competence of mammalian oocytes, the underlying mechanisms remain elusive, particularly in porcine oocytes. The present study was designed to systematically evaluate the therapeutic potential of PB2 in porcine oocyte in vitro maturation (IVM) and delineate its underlying mechanisms. Our findings reveal that supplementation with 5 μg/mL PB2 during IVM significantly improves meiotic competence, as evidenced by enhanced polar body extrusion rates, while concurrently boosting the developmental capacity of subsequent parthenogenetic embryos. PB2 reduced the incorrect distribution of cortical granules and improved the cytoplasmic maturation rate of the oocytes. Further analysis revealed that this treatment significantly enhanced the efficiency of lipid catabolism and fatty acid β-oxidation, increased the mitochondrial content and ATP levels, while reducing intra-oocyte ROS production. Notably, PB2 supplementation significantly increased the phosphorylation of AMP-activated protein kinase (AMPK); the inhibition of AMPK activity (Compound C, AMPK inhibitor) suppressed the ability of PB2 to promote lipid metabolism and increase mitochondrial content in oocytes. Besides, inhibition of AMPK lowered the oocyte maturation rate and the subsequent zygote cleavage and blastocyst formation rate when compared to that of the PB2 treatment. These results suggest that PB2 can promote lipid catabolism by activating AMPK, thereby enhancing the developmental potential of porcine oocytes.
脂肪生成和分解代谢过程构成了在卵母细胞成熟及随后的胚胎发育过程中调控能量稳态的基本代谢途径。尽管新出现的证据强调了原花青素B2(PB2)在调节哺乳动物卵母细胞减数分裂进程和发育能力方面的调控潜力,但其潜在机制仍不清楚,尤其是在猪卵母细胞中。本研究旨在系统评估PB2在猪卵母细胞体外成熟(IVM)中的治疗潜力,并阐明其潜在机制。我们的研究结果表明,在IVM期间添加5μg/mL PB2可显著提高减数分裂能力,极体排出率提高就是证明,同时还能提高后续孤雌胚胎的发育能力。PB2减少了皮质颗粒的错误分布,提高了卵母细胞的细胞质成熟率。进一步分析表明,这种处理显著提高了脂质分解代谢和脂肪酸β-氧化的效率,增加了线粒体含量和ATP水平,同时减少了卵母细胞内活性氧的产生。值得注意的是,添加PB2显著增加了AMP激活的蛋白激酶(AMPK)的磷酸化;抑制AMPK活性(化合物C,AMPK抑制剂)抑制了PB2促进脂质代谢和增加卵母细胞线粒体含量的能力。此外,与PB2处理相比,抑制AMPK降低了卵母细胞成熟率以及随后的合子分裂和囊胚形成率。这些结果表明,PB2可通过激活AMPK促进脂质分解代谢,从而增强猪卵母细胞的发育潜力。