Imbalance in the antioxidant defense system of patients with premature ovarian failure

Objective. To identify a group of the functional parameters of mitochondria associated with premature ovarian insufficiency (POI), by comparatively estimating the values of the mitochondrial function of peripheral blood mononuclear cells (MNCs) and subcutaneous fibroblasts in women with POI and preserved menstruation rhythms. Subjects and methods. The investigation enrolled 20 patients with POI and 12 women with a regular menstrual cycle at the age of 29 to 38 years. All the participants underwent physical and hormonal examinations, estimation of the membrane potential of the mitochondria of peripheral blood MNCs and subcutaneous fibroblasts, as well as the components of the antioxidant system, such as the level of total (tGSH), reduced (GSH) and oxidized (GSSG) glutathione, the ratio of reduced/oxidized glutathione (GSH/GSSG), the content of malondialdehyde (MDA), and the enzymatic activity of catalase. Results. Comparative analysis of biochemical and functional markers for endothelial dysfunction revealed significant differences in the amount of total cholesterol, apolipoprotein B, and glucose and in the level of endothelium-dependent vasodilation between the groups of women with POI and those with regular menstrual rhythms (p < 0.05). There was a significant increase in the proportion of cells with high-energy mitochondria in the women with POI versus the control group both for peripheral blood MNCs and subcutaneous fibroblasts (p < 0.05). Catalase activity was significantly lower in the POI group than in the control group (p = 0.03). A positive correlation was found between the content of MNCs and subcutaneous fibroblasts with high-energy mitochondria for both groups (r = 0.48; p = 0.029). There was also a direct correlation between MDA and the proportion of cells with high-energy mitochondria for MNCs in the POI group (r = 0.45; p = 0.043) while the control group shows an inverse correlation between MDA and apolipoproteins A1 and B (r = -0.76, p = 0.003 and r = -0.67, p = 0.012, respectively). A correlation was found between body mass index and the level of tGSH (r = 0.57, p = 0.042), reduced GSH (r = 0.57, p = 0.42), and GSH/ GSSG ratio (r = 0.66, p = 0.026) in the group of normalcy disappearing in the POI group. Conclusion. Where there are manifestations of POI, there is an imbalance between the pro- and antioxidant systems, which plays a role of the trigger of the abnormality. The prooxidant processes are mainly associated with the MNC fraction containing high-energy mitochondria. The detected differences in the development of compensatory processes for the normalcy and POI group, which consist in the breaking of the glutathione-dependent component of the antioxidant system in the abnormality, may suggest the importance of maintaining the adequate level of glutathione and possibly other free thiols in the plasma to prevent the development of this pathology.

premature ovarian insufficiency, mitochondrial dysfunction, peripheral blood mononuclear cells, glutathione-dependent component of the antioxidant system, apolipoprotein B