The State Key Laboratory of Reproductive Medicine, The Clinical Center for Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Women's Hospital School of Medicine Zhejiang University, Hangzhou, Zhejiang Province, China.
Mol Hum Reprod. 2022 May 27;28(6). doi: 10.1093/molehr/gaac018.
Endometriosis is a common disease in women of childbearing age and is closely associated with female infertility. However, the pathogenesis of endometriosis-related infertility is still not fully understood. Prohibitin 1 (PHB1), a highly conserved protein related to mitochondrial function, is differentially expressed in the endometrium of patients with endometriosis. However, the role of PHB1 in glucose metabolism in granulosa cells remains unclear. In this study, we investigated whether PHB1 expression and glucose metabolism patterns differ in the granulosa cells of patients with endometriosis and those of patients serving as controls. We then evaluated these changes after PHB1 was upregulated or downregulated in the human granulosa cell line (KGN) using a lentivirus construct. In the granulosa cells of patients with endometriosis, significantly elevated PHB1 expression, increased glucose consumption and lactic acid production, as well as aberrant expression of glycolysis-related enzymes were found compared to those without endometriosis (P < 0.05). After PHB1 expression was upregulated in KGN cells, and the expression of enzymes related to glucose metabolism, glucose consumption and lactic acid production was strikingly increased compared to controls (P < 0.05). The opposite results were found when PHB1 expression was downregulated in KGN cells. Additionally, the cell proliferation and apoptosis rates, ATP synthesis, reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were significantly altered after down-regulation of PHB1 expression in KGN cells (P < 0.05). This study suggested that PHB1 plays a pivotal role in mitigating the loss of energy caused by impaired mitochondrial function in granulosa cells of patients with endometriosis, which may explain, at least in part, why the quality of oocytes in these patients is compromised.
子宫内膜异位症是一种常见于育龄妇女的疾病，与女性不孕密切相关。然而，子宫内膜异位症相关不孕的发病机制尚不完全清楚。抑制素 1（PHB1）是一种与线粒体功能相关的高度保守蛋白，在子宫内膜异位症患者的子宫内膜中表达差异。然而，PHB1 在颗粒细胞中的葡萄糖代谢中的作用尚不清楚。在这项研究中，我们研究了子宫内膜异位症患者和对照组患者的颗粒细胞中 PHB1 表达和葡萄糖代谢模式是否不同。然后，我们使用慢病毒构建物评估了在人颗粒细胞系（KGN）中上调或下调 PHB1 后这些变化。与无子宫内膜异位症的患者相比，子宫内膜异位症患者的颗粒细胞中 PHB1 表达显著升高，葡萄糖消耗和乳酸生成增加，以及糖酵解相关酶的异常表达（P<0.05）。在 KGN 细胞中上调 PHB1 表达后，与对照组相比，与葡萄糖代谢、葡萄糖消耗和乳酸生成相关的酶的表达明显增加（P<0.05）。在 KGN 细胞中下调 PHB1 表达时，发现相反的结果。此外，下调 KGN 细胞中 PHB1 表达后，细胞增殖和凋亡率、ATP 合成、活性氧（ROS）水平和线粒体膜电位（MMP）显著改变（P<0.05）。这项研究表明，PHB1 在减轻颗粒细胞中线粒体功能受损导致的能量损失方面发挥着关键作用，这至少可以部分解释为什么这些患者的卵母细胞质量受损。
