PDF(Pubmed)
Abstract：
Advanced glycation end products (AGEs) are the final products of the Maillard reaction, formed through the interaction of carbohydrates and proteins. Reactive dicarbonyl compounds such as methylglyoxal (MGO) serve as precursors for AGEs formation. Elevated levels of MGO/AGEs are observed in conditions like obesity, polycystic ovarian syndrome (PCOS), and diabetes, negatively impacting oocyte development. Previous studies have shown that hydrogen sulfide, a gasotransmitter with anti-AGEs effects, is produced in a process influenced by vitamin B6. R-α-lipoic acid (ALA) inhibits protein glycation and AGEs formation while stimulating glutathione (GSH) production. Taurine mitigates oxidative stress and acts as an anti-glycation compound, preventing in vitro glycation and AGEs accumulation. This study aimed to explore the ameliorative effects of a micronutrient support (Taurine, ALA and B6: TAB) on mouse oocytes challenged with MGO. Our results indicate that MGO reduces oocyte developmental competence, while TAB supplementation improves maturation, fertilization, and blastocyst formation rates. TAB also restores cell lineage allocation, redox balance and mitigates mitochondrial dysfunction in MGO-challenged oocytes. Furthermore, cumulus cells express key enzymes in the transsulfuration pathway, and TAB enhances their mRNA expression. However, TAB does not rescue MGO-induced damage in denuded oocytes, emphasizing the supportive role of cumulus cells. Overall, these findings suggest that TAB interventions may have significant implications for addressing reproductive dysfunctions associated with elevated MGO/AGEs levels. This study highlights the potential of TAB supplementation in preserving the developmental competence of COCs exposed to MGO stress, providing insights into mitigating the impact of dicarbonyl stress on oocyte quality and reproductive outcomes.
摘要：
晚期糖基化终产物（AGEs）是美拉德反应的最终产物，通过碳水化合物和蛋白质的相互作用形成。反应性二羰基化合物如甲基乙二醛(MGO)用作AGEs形成的前体。在肥胖等疾病中观察到MGO/AGEs水平升高，多囊卵巢综合征(PCOS),糖尿病,对卵母细胞发育产生负面影响。以前的研究表明，硫化氢，具有抗AGEs作用的气体发射器，在受维生素B6影响的过程中产生。R-α-硫辛酸(ALA)抑制蛋白质糖基化和AGEs形成,同时刺激谷胱甘肽(GSH)产生。牛磺酸缓解氧化应激，并作为抗糖基化化合物，防止体外糖基化和AGEs积累。本研究旨在探讨微量营养素支持（牛磺酸，ALA和B6：TAB）对用MGO攻击的小鼠卵母细胞。我们的结果表明MGO降低了卵母细胞的发育能力，虽然TAB补充可以改善成熟，受精,和胚泡形成率。TAB还恢复细胞谱系分配，氧化还原平衡并减轻MGO攻击卵母细胞的线粒体功能障碍。此外，卵丘细胞表达转硫途径的关键酶，和TAB增强它们的mRNA表达。然而,TAB不能挽救MGO诱导的剥脱卵母细胞损伤，强调卵丘细胞的支持作用。总的来说,这些研究结果表明,TAB干预可能对解决与MGO/AGEs水平升高相关的生殖功能障碍具有重要意义.这项研究强调了TAB补充剂在保持暴露于MGO压力的COCs发育能力方面的潜力，为减轻二羰基应激对卵母细胞质量和生殖结果的影响提供见解。
