Mitochondrial Morphology and Function Abnormality in Ovarian Granulosa Cells of Patients with Diminished Ovarian Reserve.

ABSTRACT

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.