摘要
Within the antral follicle, the oocyte is reliant on metabolic support from its surrounding somatic cells. Metabolism plays a critical role in oocyte developmental competence (oocyte quality). In the last decade, there has been significant progress in understanding the metabolism of the cumulus–oocyte complex (COC) during its final stages of growth and maturation in the follicle. Certain metabolic conditions (e.g. obesity) or ART (e.g. IVM) perturb COC metabolism, providing insights into metabolic regulation of oocyte quality.This review provides an update on the progress made in our understanding of COC metabolism, and the metabolic conditions that influence both meiotic and developmental competence of the oocyte.The PubMed database was used to search for peer-reviewed original and review articles. Searches were performed adopting the main terms ‘oocyte metabolism’, ‘cumulus cell metabolism’, ‘oocyte maturation’, ‘oocyte mitochondria’, ‘oocyte metabolism’, ‘oocyte developmental competence’ and ‘oocyte IVM’.Metabolism is a major determinant of oocyte quality. Glucose is an essential requirement for both meiotic and cytoplasmic maturation of the COC. Glucose is the driver of cumulus cell metabolism and is essential for energy production, extracellular matrix formation and supply of pyruvate to the oocyte for ATP production. Mitochondria are the primary source of ATP production within the oocyte. Recent advances in real-time live cell imaging reveal dynamic fluctuations in ATP demand throughout oocyte maturation. Cumulus cells have been shown to play a central role in maintaining adequate oocyte ATP levels by providing metabolic support through gap junctional communication. New insights have highlighted the importance of oocyte lipid metabolism for oocyte oxidative phosphorylation for ATP production, meiotic progression and developmental competence. Within the last decade, several new strategies for improving the developmental competence of oocytes undergoing IVM have emerged, including modulation of cyclic nucleotides, the addition of precursors for the antioxidant glutathione or endogenous maturation mediators such as epidermal growth factor-like peptides and growth differentiation factor 9/bone morphogenetic protein 15. These IVM additives positively alter COC metabolic endpoints commonly associated with oocyte competence. There remain significant challenges in the study of COC metabolism. Owing to the paucity in non-invasive or in situ techniques to assess metabolism, most work to date has used in vitro or ex vivo models. Additionally, the difficulty of measuring oocyte and cumulus cell metabolism separately while still in a complex has led to the frequent use of denuded oocytes, the results from which should be interpreted with caution since the oocyte and cumulus cell compartments are metabolically interdependent, and oocytes do not naturally exist in a naked state until after fertilization. There are emerging tools, including live fluorescence imaging and photonics probes, which may provide ways to measure the dynamic nature of metabolism in a single oocyte, potentially while in situ.There is an association between oocyte metabolism and oocyte developmental competence. Advancing our understanding of basic cellular and biochemical mechanisms regulating oocyte metabolism may identify new avenues to augment oocyte quality and assess developmental potential in assisted reproduction.
摘要译文
在窦囊中，卵母细胞依赖于其周围体细胞的代谢支持。代谢在卵母细胞发育能力（卵母细胞质量）中起着至关重要的作用。在过去的十年中，在卵泡生长和成熟的最后阶段，卵丘-卵母细胞复合物（COC）的代谢有了重要的了解。某些代谢条件（例如肥胖）或ART（例如IVM）扰乱了COC代谢，提供了对卵母细胞质量的代谢调节的见解。该综述提供了我们对COC代谢的理解以及影响卵母细胞减数分裂和发育能力的代谢条件的最新进展。PubMed数据库是用于搜索同伴-已审阅的原始文章和评论文章。进行搜索的主要术语是“卵母细胞代谢”，“卵细胞代谢”，“卵母细胞成熟”，“卵母细胞线粒体”，“卵母细胞代谢”，“卵母细胞发育能力”和“卵母细胞IVM”。卵母细胞质量。葡萄糖是COC减数分裂和细胞质成熟的基本要求。葡萄糖是卵丘细胞代谢的驱动力，对于能量产生，细胞外基质形成以及丙酮酸向卵母细胞供应以产生ATP至关重要。线粒体是卵母细胞中ATP产生的主要来源。实时活细胞成像的最新进展揭示了整个卵母细胞成熟过程中ATP需求的动态波动。已经显示，通过间隙连接通讯提供代谢支持，积淀细胞在维持足够的卵母细胞ATP水平中起着核心作用。新的见解突出了卵母细胞脂质代谢对于卵母细胞氧化磷酸化对于ATP产生，减数分裂进程和发育能力的重要性。在过去的十年中，已经出现了几种改善经历IVM的卵母细胞发育能力的新策略，包括调节环核苷酸，添加抗氧化剂谷胱甘肽的前体或内源性成熟介质，例如表皮生长因子（如肽和生长分化因子） 9 /骨形态发生蛋白15。这些IVM添加剂可积极改变通常与卵母细胞能力相关的COC代谢终点。在COC代谢研究中仍然存在重大挑战。由于缺乏用于评估代谢的非侵入性或原位技术，迄今为止，大多数工作已使用体外或离体模型。另外，难以测量仍然处于复杂状态的卵母细胞和卵丘细胞新陈代谢的困难，导致频繁使用裸露的卵母细胞，由于卵母细胞和卵丘细胞区隔在代谢上是相互依赖的，因此应谨慎解释其结果，卵母细胞确实直到受精后才能裸露自然存在。有新兴的工具，包括实时荧光成像和光子探针，它们可能提供方法来测量单个卵母细胞潜在地原位代谢的动态特性。卵母细胞代谢与卵母细胞发育能力之间存在关联。推进我们对调节卵母细胞代谢的基本细胞和生化机制的理解，可能会发现提高卵母细胞质量并评估辅助生殖发育潜力的新途径。
Dulama Richani [1]; Kylie R Dunning [2]; Jeremy G Thompson [2]; Robert B Gilchrist [1]. Metabolic co-dependence of the oocyte and cumulus cells: essential role in determining oocyte developmental competence[J]. Human Reproduction Update, 2021,27(1): 27-47