Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Fertility Research Centre, Fatemieh Hospital, Hamadan University of Medical Sciences, Hamadan, Iran.
J Assist Reprod Genet. 2023 Feb;40(2):343-359. doi: 10.1007/s10815-022-02676-w. Epub 2023 Jan 3.
We hypothesized that immature oocytes are associated with impaired energy production in surrounding granulosa cells (GCs) in polycystic ovary syndrome (PCOS). Thus, this study investigated mitochondrial function, determined expression of glycolytic regulatory enzymes, and measured ATP levels in GCs of PCOS patients.
GCs were isolated from forty-five PCOS patients and 45 control women. Intracellular concentration of reactive oxygen species (ROS), mitochondrial membrane potential (Δψ), the rate of glycolysis, total antioxidant capacity (TAC), activities of catalase (CAT) and superoxide dismutase (SOD), and ATP level were measured in GCs. The gene expression and protein levels of glycolytic enzymes (hexokinase, muscular phosphofructokinase, platelet derived phosphofructokinase, and muscular pyruvate kinase) were determined. Association of GC energy level with oocyte maturation was further validated by measuring glycolysis rate and ATP level in GCs isolated from mature and immature follicles from new set of fifteen PCOS patients and 15 controls.
PCOS patients showed higher ROS level, decreased TAC, reduced CAT and SOD activities, and lower Δψ together with reduced expression of key glycolytic enzymes. ATP concentration and biochemical pregnancy were lower in PCOS compared with control group. ATP levels were found to be significantly correlated with ROS and Δψ (r = - 0.624 and r = 0.487, respectively). GCs isolated from immature follicles had significantly lower ATP levels and rate of glycolysis compared with the GCs separated from mature follicles in both PCOS patients and control.
Declined energy due to the mitochondrial dysfunction and restrained glycolysis in GCs is associated with the immature oocytes and lower biochemical pregnancy in PCOS.
我们假设多囊卵巢综合征（PCOS）患者的不成熟卵母细胞与周围颗粒细胞（GCs）的能量产生受损有关。因此，本研究调查了 PCOS 患者 GCs 的线粒体功能、糖酵解调节酶的表达，并测量了 ATP 水平。
从 45 名 PCOS 患者和 45 名对照女性中分离 GCs。测量 GCs 中的活性氧（ROS）浓度、线粒体膜电位（Δψ）、糖酵解速率、总抗氧化能力（TAC）、过氧化氢酶（CAT）和超氧化物歧化酶（SOD）的活性以及 ATP 水平。测定糖酵解酶（己糖激酶、肌型磷酸果糖激酶、血小板衍生磷酸果糖激酶和肌型丙酮酸激酶）的基因表达和蛋白水平。通过测量新的 15 名 PCOS 患者和 15 名对照患者成熟和不成熟卵泡中 GCs 的糖酵解速率和 ATP 水平，进一步验证了 GCs 能量水平与卵母细胞成熟的相关性。
与对照组相比，PCOS 患者的 ROS 水平升高，TAC 降低，CAT 和 SOD 活性降低，Δψ 降低，关键糖酵解酶的表达降低。与对照组相比，PCOS 组的 ATP 浓度和生化妊娠率较低。ATP 水平与 ROS 和 Δψ 呈显著负相关（r = -0.624 和 r = 0.487）。与对照组相比，PCOS 患者和对照组的不成熟卵泡分离的 GCs 的 ATP 水平和糖酵解速率均显著降低。
GCs 中线粒体功能障碍和糖酵解受到抑制导致的能量下降与 PCOS 中的不成熟卵母细胞和较低的生化妊娠有关。
