Hebei Key Laboratory of Reproductive Medicine, Hebei Reproductive Health Hospital, Hebei Institute of Reproductive Health Science and Technology, No. 480 Heping Road, Xinhua District, Shijiazhuang, 050071, China.
Hebei Medical University, No. 361 Zhongshan Road, Chang'An District, Shijiazhuang, 050017, China.
Reprod Sci. 2024 Jul;31(7):2009-2020. doi: 10.1007/s43032-024-01459-1. Epub 2024 Jan 31.
In this study, we examined the changes in the mitochondrial structure and function in cumulus granulosa cells of patients with diminished ovarian reserve (DOR) to explore the causes and mechanisms of decreased mitochondrial quality. The mitochondrial ultrastructure was observed by transmission electron microscope, and the function was determined by detecting the ATP content, reactive oxygen species (ROS) levels, the number of mitochondria, and the mitochondrial membrane potential. The expression of ATP synthases in relation to mitochondrial function was analyzed. Additionally, protein immunoblotting was used to compare the expression levels of mitochondrial kinetic protein, the related channel protein in the two groups. Patients with DOR had abnormal granulosa cell morphology, increased mitochondrial abnormalities, decreased mitochondrial function, and disturbed mitochondrial dynamics. Additionally, the silent information regulator 1 (SIRT1)/phospho-AMP-activated protein kinase (P-AMPK)-peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) pathway expression was decreased, which was speculated to be associated with the decreased mitochondrial mass in the DOR group. The mitochondrial mass was decreased in granulosa cells of patients in the DOR group. The mitochondrial dysfunction observed in granulosa cells of patients in the DOR group may be associated with dysregulation of the SIRT1/P-AMPK-PGC-1α-mitochondrial transcription factor A (TFAM) pathway.
在这项研究中,我们研究了卵巢储备功能减退(DOR)患者的卵丘颗粒细胞中线粒体结构和功能的变化,以探讨线粒体质量下降的原因和机制。通过透射电子显微镜观察线粒体超微结构,通过检测 ATP 含量、活性氧(ROS)水平、线粒体数量和线粒体膜电位来确定线粒体功能。分析与线粒体功能相关的 ATP 合酶的表达。此外,还通过蛋白质免疫印迹比较两组中线粒体动力学蛋白和相关通道蛋白的表达水平。DOR 患者的颗粒细胞形态异常,线粒体异常增加,线粒体功能下降,线粒体动力学紊乱。此外,沉默信息调节因子 1(SIRT1)/磷酸腺苷激活蛋白激酶(P-AMPK)-过氧化物酶体增殖物激活受体-γ共激活因子 1α(PGC-1α)通路表达降低,推测与 DOR 组中线粒体质量下降有关。DOR 组颗粒细胞中线粒体质量减少。DOR 组颗粒细胞中线粒体功能障碍可能与 SIRT1/P-AMPK-PGC-1α-线粒体转录因子 A(TFAM)通路失调有关。