Age-related changes in the mitochondria of human mural granulosa cells

Abstract

What changes in the mitochondria of human mural granulosa cells (mGCs) with maternal aging? The mitochondrial membrane potential (MMP) and the ability of oxidative phosphorylation (OXPHOS) of mGCs declines with reproductive aging, accompanied with more abnormal mitochondria. Mitochondria play an important role in the dialogue between the mGCs and oocytes. However, the underlying mechanism of mitochondrial dysfunction in mGCs in aging is still poorly understood. In total, 149 infertile women underwent IVF in the ART Centre of the Chinese PLA General Hospital, China from September 2016 to May 2017. Two age groups were investigated: the young group (P = 0.012). mtDNA relative copy number was positively correlated with maternal age (r = 0.294, P = 0.009) and we found no one with 4977-bp deleted mitochondria. JC-1 (dye used as an indicator of MMP) ratio in the old group was significantly lower than the young group (3.01 ± 0.21 vs 3.85 ± 0.27, P = 0.033). Intracellular ROS levels between the groups did not differ significantly (P = 0.191). The intracellular ATP level in the young group was 1.75-fold higher than that of the advanced-age group (7.17 ± 1.16 vs 4.15 ± 0.60, P = 0.025). The protein expression of ATP5A1, as one of five proteins of OXPHOS, decreased with aging (P < 0.001). ATP5A1 mRNA expression was negatively correlated with aging (r = −0.341, P = 0.012). The quantity of mGCs from some individual patient, especially an advanced-age individual, was small, which cannot meet the demands of all the detections. mGCs dysfunction with aging is mainly linked to impaired mitochondrial function, especially OXPHOS function. Improving the OXPHOS ability in mGCs should be the focus in resolving infertility among advanced age women and making mGCs the proper mitochondria donor cells in the autologous mitochondria transplantation to oocytes. This work was supported by the grants of the National High Technology Research and Development Program of China, 863 Program No. SS2015AA020402, and the Key Projects of Military Medical Research, No. BWS11J058. There were no competing interests.