Antioxidant Defense Expressed as Glutathione Status and Keap1-Nrf2 System Action in Relation to Anthropometric Parameters and Body Composition in Young Women with Polycystic Ovary Syndrome

Abstract

Metabolic disorders present in women with polycystic ovary syndrome (PCOS) and the associated risk of obesity may result in increased oxidative stress and reproductive failure. Therefore, we evaluated the concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione peroxidase (GPx), and reductase (GR), as well as nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associating protein1 (Keap1) in the serum of 56 women with PCOS divided according to the visceral to subcutaneous fat surface ratio (VAT/SAT) and waist-to-hip ratio (WHR) values. Antioxidant parameter levels were measured by competitive inhibition enzyme immunoassay technique. As the VAT/SAT ratio and WHR increased, we observed significantly higher concentrations of GSSG and Keap1 protein and a lower value of the GSSG/GSH ratio (R-index), which is considered an index of cellular redox (p < 0.05). Negative correlations were found between the R-index and body weight, BMI, WHR, subcutaneous and visceral fat surface and the VAT/SAT ratio, and total body fat; positive links were found with fat free mass and total body water. Opposite associations were noted between GSSG level and the aforementioned body composition parameters. Oxidative stress characterized by a depleted reduced-to-oxidized glutathione index is associated with anthropometric and body composition parameters in women with PCOS. In particular, abdominal obesity expressed by the VAT/SAT ratio and/or WHR seems to have a negative impact on glutathione status, which may lead to a disruption of many biological cell processes. The observed negative association of Keap1 with R-index suggests that the elevated oxidative changes dependent on the VAT/SAT ratio may lead to Nrf2 activation to promote antioxidant enzyme expression. Although the GSH/GSSG index as well as the VAT/SAT ratio appear to be good indicators of oxidative status, studies on a larger group of patients should continue to confirm these links among women with PCOS.

Mechanisms and Target Parameters in Relation to Polycystic Ovary Syndrome and Physical Exercise: Focus on the Master Triad of Hormonal Changes, Oxidative Stress, and Inflammation

“…Sulaiman et al demonstrated a lower GSH level in women with PCOS compared to healthy women [ 8 ]. These results support the conclusions reached by other researchers, such as Chelchowska et al, whose findings showed a reduction of up to 50% in glutathione levels in women with PCOS compared to healthy individuals [ 77 ].…”

Role of nuclear factor erythroid 2-related factor 2 (Nrf2) in female and male fertility

“…Some investigations have shown the role of therapeutic agents in preserving the adipose cells under PCOS through the promotion of Nrf2/HO-1/Cyp1b1 [ 70 ]. The level of GSSG and Keap1 protein concentrations shows a higher positive correlation between PCOS patients and low concentration of Keap1 in the visceral fat surface compared to the subcutaneous fat surface, which may also lead to the activation of the Nrf2 and its downstream genes [ 71 ]. There are strong beliefs that claim PCOS can lead to not only infertility but also some other induced behaviors such as short-term memory impairment, depression, and anxiety.…”

“… Female infertility disorders Type of study Models of disorder Outcomes References PCOS In Vivo (most of them) In Vitro Animal (rat and mice) and Human models The use of different antioxidant compounds can modulate the decrease in the expression of Nrf2 and its downstream genes, including HO-1 and NQO1, which is caused by oxidative stress in PCOS. [ [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] ] Endometriosis In Vitro In vivo Animal (Rat and Mice) and human model Endometriotic ectopic lesions show a decrease in Nrf2, GCL (an enzyme involved in glutathione synthesis) and its downstream molecules (NQO1, HO-1) compared to eutopic endometria [ 74 , 75 , 76 ] POF (POI) In Vivo Animal (Rat and Mice) models Oxidative stress is manifested by the decrease of ovarian oxidation markers such as SOD- and GSH- and the increase of MDA in the ovarian tissue of POI models, consequently, the expression level of Keap-1 in the ovarian tissue is increased, while the expression level of Nrf2/HO-1 and other downstream genes including GCLC and NQO1 decreases. In this regard, the use of different antioxidant compounds by activating Nrf2/ARE signaling pathway leads to the improvement of antioxidant activity and the enhancement of ovarian reserve in POI.…”

Abdominal Obesity in Women with Polycystic Ovary Syndrome and Its Relationship with Diet, Physical Activity and Insulin Resistance: A Pilot Study

“…Visceral adipose tissue is regarded to cause disturbances in insulin signaling in women with PCOS and increase lipolysis, which encourages IR [ 3 ]. Additionally, excess abdominal adipose tissue is associated with low-grade chronic inflammation, which is another important element in the pathogenesis of IR in this endocrinopathy [ 20 , 21 , 22 ].…”