Division of Applied Life Science (BK21 Four), Gyeongsang National University, Jinju 52828, Korea.
Department of Therapeutic Chemistry, Division of Pharmaceutical and Drug Industries Research, National Research Centre (NRC), Dokki, Cairo 12622, Egypt.
Int J Mol Sci. 2020 Dec 26;22(1):168. doi: 10.3390/ijms22010168.
Juglone, a major naphthalenedione component of walnut trees, has long been used in traditional medicine as an antimicrobial and antitumor agent. Nonetheless, its impact on oocyte and preimplantation embryo development has not been entirely clarified. Using the bovine model, we sought to elucidate the impact of juglone treatment during the in vitro maturation (IVM) of oocytes on their maturation and development of embryos. Results showed a severe reduction in oocyte nuclear maturation and cumulus expansion and a significant increase in mitochondrial dysfunction and reactive oxygen species (ROS) levels in cumulus-oocyte complexes (COCs) treated with juglone (12.5, 25.0, and 50.0 µM). In addition, RT-qPCR showed downregulation of the expansion-related (HAS2, TNFAIP6, PTX3, and PTGS2) and mitochondrial (ATPase6 and ATP5F1E) genes in juglone-treated COCs. Moreover, the development rates of day 4 total cleavage and 8-16 cell stage embryos, as well as day 8 blastocysts, were significantly reduced following exposure to juglone. Using immunofluorescence, the apoptotic marker caspase-9 was overexpressed in oocytes exposed to juglone (25.0 µM) compared to the untreated control. In conclusion, our study reports that exposing bovine oocytes to 12.5-50.0 µM of juglone can reduce their development through the direct induction of ROS accumulation, apoptosis, and mitochondrial dysfunction.
胡桃醌是核桃树中一种主要的萘醌成分，长期以来一直被传统医学用作抗菌和抗肿瘤药物。尽管如此，其对卵母细胞和植入前胚胎发育的影响尚未完全阐明。我们使用牛模型，试图阐明在卵母细胞体外成熟（IVM）期间用胡桃醌处理对卵母细胞成熟和胚胎发育的影响。结果表明，用胡桃醌（12.5、25.0 和 50.0 μM）处理的卵母细胞和卵丘-卵母细胞复合物（COCs）的核成熟和卵丘扩展严重减少，线粒体功能障碍和活性氧（ROS）水平显著增加。此外，RT-qPCR 显示，在胡桃醌处理的 COCs 中，与扩展相关的（HAS2、TNFAIP6、PTX3 和 PTGS2）和线粒体（ATPase6 和 ATP5F1E）基因下调。此外，暴露于胡桃醌后，第 4 天总卵裂和 8-16 细胞期胚胎以及第 8 天囊胚的发育率显著降低。通过免疫荧光，与未经处理的对照组相比，暴露于胡桃醌（25.0 μM）的卵母细胞中凋亡标志物 caspase-9 过度表达。总之，我们的研究报告称，将牛卵母细胞暴露于 12.5-50.0 μM 的胡桃醌中可以通过直接诱导 ROS 积累、凋亡和线粒体功能障碍来降低其发育能力。
