Follicular microenvironment is paramount in the acquisition of oocyte competence, which is dependent on two interconnected and interdependent processes: nuclear and cytoplasmic maturation. Extensive research conducted in human and model systems has provided evidence that those processes are disturbed with female aging. In fact, advanced maternal age (AMA) is associated with a lower chance of pregnancy and live birth, explained by the age-related decline in oocyte quality/competence. This decline has largely been attributed to mitochondria, essential for oocyte maturation, fertilization, and embryo development; with mitochondrial dysfunction leading to oxidative stress, responsible for nuclear and mitochondrial damage, suboptimal intracellular energy levels, calcium disturbance, and meiotic spindle alterations, that may result in oocyte aneuploidy. Nuclear-related mechanisms that justify increased oocyte aneuploidy include deoxyribonucleic acid (DNA) damage, loss of chromosomal cohesion, spindle assembly checkpoint dysfunction, meiotic recombination errors, and telomere attrition. On the other hand, age-dependent cytoplasmic maturation failure is related to mitochondrial dysfunction, altered mitochondrial biogenesis, altered mitochondrial morphology, distribution, activity, and dynamics, dysmorphic smooth endoplasmic reticulum and calcium disturbance, and alterations in the cytoskeleton. Furthermore, reproductive somatic cells also experience the effects of aging, including mitochondrial dysfunction and DNA damage, compromising the crosstalk between granulosa/cumulus cells and oocytes, also affected by a loss of gap junctions. Old oocytes seem therefore to mature in an altered microenvironment, with changes in metabolites, ribonucleic acid (RNA), proteins, and lipids. Overall, understanding the mechanisms implicated in the loss of oocyte quality will allow the establishment of emerging biomarkers and potential therapeutic anti-aging strategies.

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衰老和卵母细胞能力：分子细胞视角

卵泡微环境对于卵母细胞能力的获得至关重要，这取决于两个相互关联且相互依赖的过程：核成熟和细胞质成熟。对人体和模型系统进行的广泛研究提供的证据表明，这些过程会因女性衰老而受到干扰。事实上，高龄产妇 (AMA) 与怀孕和活产的机会较低有关，原因是卵母细胞质量/能力与年龄有关。这种下降主要归因于线粒体，它对于卵母细胞成熟、受精和胚胎发育至关重要。线粒体功能障碍导致氧化应激，导致核和线粒体损伤、细胞内能量水平欠佳、钙紊乱和减数分裂纺锤体改变，可能导致卵母细胞非整倍体。证明卵母细胞非整倍性增加的核相关机制包括脱氧核糖核酸 (DNA) 损伤、染色体内聚力丧失、纺锤体组装检查点功能障碍、减数分裂重组错误和端粒磨损。另一方面，年龄依赖性细胞质成熟失败与线粒体功能障碍、线粒体生物合成改变、线粒体形态、分布、活性和动力学改变、平滑内质网畸形和钙紊乱以及细胞骨架的改变有关。此外，生殖体细胞也会受到衰老的影响，包括线粒体功能障碍和 DNA 损伤，从而损害颗粒/卵丘细胞和卵母细胞之间的串扰，也受到间隙连接丢失的影响。因此，老卵母细胞似乎在改变的微环境中成熟，代谢物、核糖核酸（RNA）、蛋白质和脂质发生变化。总体而言，了解卵母细胞质量损失的机制将有助于建立新兴的生物标志物和潜在的抗衰老治疗策略。