Decline in ovarian reserve with aging is associated with reduced fertility and the development of metabolic abnormalities. Once mitochondrial homeostasis is imbalanced, it may lead to poor reproductive cell quality and aging. However, Phosphoglycerate translocase 5 (PGAM5), located in the mitochondrial membrane, is associated with necroptosis, apoptosis, and mitophagy, although the underlying mechanisms associated with ovarian aging remain unknown. Therefore, we attempted to uncover whether the high phosphoglycerate mutant enzyme family member 5 (PGAM5) expression is associated with female infertility in cumulus cells, and aims to find out the underlying mechanism of action of PGAM5. We found that PGAM5 is highly expressed and positively associated with aging, and has the potential to help maintain and regulate mitochondrial dynamics and metabolic reprogramming in aging granulosa cells, ovaries of aged female mice, and elderly patients. PGAM5 undergoes activation in the aging group and translocated to the outer membrane of mitochondria, co-regulating DRP1; thereby increasing mitochondrial fission. A significant reduction in the quality of mitochondria in the aging group, a serious imbalance, and a significant reduction in energy, causing metabolism shift toward glycolysis, were also reported. Since PGAM5 is eliminated, the mitochondrial function and metabolism of aging cells are partially reversed. A total of 70 patients undergoing in vitro fertilization (IVF) treatment were recruited in this clinical study. The high expression of PGAM5 in the cumulus cells is negatively correlated with the pregnancy rate of infertile patients. Hence, PGAM5 has immense potential to be used as a diagnostic marker.

中文翻译：

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磷酸甘油酸变位酶家族成员 5 在衰老过程中通过线粒体动态重排维持卵母细胞质量

卵巢储备随着年龄的增长而下降与生育能力下降和代谢异常的发展有关。一旦线粒体稳态失衡，可能会导致生殖细胞质量差和衰老。然而，位于线粒体膜中的磷酸甘油酸转位酶 5 (PGAM5) 与坏死性凋亡、细胞凋亡和线粒体自噬有关，尽管与卵巢衰老相关的潜在机制仍然未知。因此，我们试图揭示卵丘细胞中高磷酸甘油酸突变酶家族成员 5 (PGAM5) 的表达是否与女性不育有关，并旨在找出 PGAM5 的潜在作用机制。我们发现 PGAM5 高度表达并与衰老呈正相关，并且有可能帮助维持和调节衰老颗粒细胞、老年雌性小鼠卵巢和老年患者的线粒体动力学和代谢重编程。PGAM5 在衰老组中被激活并转移到线粒体外膜，共同调节 DRP1；从而增加线粒体裂变。还报道了衰老组线粒体质量显着降低，严重失衡，能量显着降低，导致新陈代谢转向糖酵解。由于 PGAM5 被消除，衰老细胞的线粒体功能和代谢被部分逆转。本临床研究共招募了 70 名接受体外受精 (IVF) 治疗的患者。PGAM5在卵丘细胞中的高表达与不孕症患者的妊娠率呈负相关。因此，PGAM5 具有作为诊断标志物的巨大潜力。