Oxidative Stress In Polycystic Ovary Syndrome Research Articles

Melatonin attenuates hepatic oxidative stress by regulating the P62/LC3 autophagy pathway in PCOS.

The elevated level of hepatic oxidative stress (OS) in polycystic ovary syndrome (PCOS) is one of the important causes of liver abnormalities. Therefore, decreasing the level of hepatic OS in PCOS is beneficial to reduce the risk of PCOS-related liver diseases. Melatonin (MT), recognized as a potent antioxidant. Nevertheless, the efficacy of MT in alleviating hepatic OS associated with PCOS is yet to be established, and the precise mechanisms through which MT exerts its antioxidant effects remain to be fully elucidated. The aim of this study was to explore the potential mechanism by which MT reduces hepatic OS in PCOS. First, we detected elevated OS levels in the PCOS samples. Subsequently, with MT pretreatment, we discovered that MT could significantly diminish the levels of OS, liver triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT) andaspartate aminotransferase (AST)，while concurrently ameliorating mitochondrial structural damage in PCOS liver. Furthermore, we identified elevated autophagy levels in the liver of PCOS rats and an inhibition of the Keap1-Nrf2 pathway. Through MT pretreatment, the expression of LC3 was significantly decreased, while the Keap1-Nrf2 pathway was activated. Our study showed that MT could affect the Nrf2 pathway dependent on the P62/LC3 autophagy pathway, thereby attenuating hepatic OS in PCOS. These findings offer novel insights and research avenues for the study of PCOS-related liver diseases.

Granulosa cell insight: unraveling the potential of menstrual blood-derived stem cells and their exosomes on mitochondrial mechanisms in polycystic ovary syndrome (PCOS)

BackgroundPolycystic ovary syndrome (PCOS) presents a significant challenge in women’s reproductive health, characterized by disrupted folliculogenesis and ovulatory dysfunction. Central to PCOS pathogenesis are granulosa cells, whose dysfunction contributes to aberrant steroid hormone production and oxidative stress. Mitochondrial dysfunction emerges as a key player, influencing cellular energetics, oxidative stress, and steroidogenesis. This study investigates the therapeutic potential of menstrual blood-derived stem cells (MenSCs) and their exosomes in mitigating mitochondrial dysfunction and oxidative stress in PCOS granulosa cells.MethodsUsing a rat model of PCOS induced by letrozole, granulosa cells were harvested and cultured. MenSCs and their exosomes were employed to assess their effects on mitochondrial biogenesis, oxidative stress, and estrogen production in PCOS granulosa cells.ResultsResults showed diminished mitochondrial biogenesis and increased oxidative stress in PCOS granulosa cells, alongside reduced estrogen production. Treatment with MenSCs and their exosomes demonstrated significant improvements in mitochondrial biogenesis, oxidative stress levels, and estrogen production in PCOS granulosa cells. Further analysis showed MenSCs' superior efficacy over exosomes, attributed to their sustained secretion of bioactive factors. Mechanistically, MenSCs and exosomes activated pathways related to mitochondrial biogenesis and antioxidative defense, highlighting their therapeutic potential for PCOS.ConclusionsThis study offers insights into granulosa cells mitochondria’s role in PCOS pathogenesis and proposes MenSCs and exosomes as a potential strategy for mitigating mitochondrial dysfunction and oxidative stress in PCOS. Further research is needed to understand underlying mechanisms and validate clinical efficacy, presenting promising avenues for addressing PCOS complexity.

Ameliorating effects of adropin on letrozole-induced polycystic ovary syndrome via regulating steroidogenesis and the microbiota inflammatory axis in rats.

Growing evidence supports the role of gut microbiota in chronic inflammation, insulin resistance (IR) and sex hormone production in polycystic ovary syndrome (PCOS). Adropin plays a pivotal role in the regulation of glucose and lipid metabolism and is negatively correlated with IR, which affects intestinal microbiota and sex hormones. However, the effect of adropin administration in PCOS has yet to be investigated. The present study aimed to assess the effects of adropin on letrozole (LTZ)-induced PCOS in rats and the potential underlying mechanisms. The experimental groups were normal, adropin, letrozole and LTZ+adropin. At the end of the experiment, adropin significantly ameliorated PCOS, as evidenced by restoring the normal ovarian structure, decreasing the theca cell thickness in antral follicles, as well as serum testosterone and luteinizing hormone levels and luteinizing hormone/follicle-stimulating hormone ratios, at the same time as increasing granulosa cell thickness in antral follicles, oestradiol and follicle-stimulating hormone levels. The ameliorating effect could be attributed to its effect on sex hormone-binding globulin, key steroidogenic genes STAR and CYP11A1, IR, lipid profile, gut microbiota metabolites-brain-ovary axis components (short chain fatty acids, free fatty acid receptor 3 and peptide YY), intestinal permeability marker (zonulin and tight junction protein claudin-1), lipopolysaccharides/Toll-like receptor 4/nuclear factor kappa B inflammatory pathway and oxidative stress makers (malondialdehyde and total antioxidant capacity). In conclusion, adropin has a promising therapeutic effect on PCOS by regulating steroidogenesis, IR, lipid profile, the gut microbiota inflammatory axis and redox homeostasis. KEY POINTS: Adropin treatment reversed endocrine and ovarian morphology disorders in polycystic ovary syndrome (PCOS). Adropin regulated the ovarian steroidogenesis and sex hormone-binding globulin in PCOS. Adropin improved lipid profile and decreased insulin resistance in PCOS. Adropin modulated the components of the gut-brain-ovary axis (short chain fatty acids, free fatty acid receptor 3 and peptide YY) in PCOS. Adropin improved intestinal barrier integrity, suppressed of lipopolysaccharides/Toll-like receptor 4/nuclear factor kappa B signalling pathway and oxidative stress in PCOS.

Exploring the Therapeutic Potential of Sodium Hydrosulfide in Alleviating Oxidative Stress and Ovarian Dysfunction in a Rat Model of Polycystic Ovary Syndrome.

Oxidative stress is known to play a key role in the occurrence of polycystic ovary syndrome (PCOS) as the most common cause of anovulatory infertility. The purpose of the current study was to investigate whether diminished activity of ovarian enzymes responsible for hydrogen sulfide (H2S) production, cystathionine β-synthase (CBS), and cystathionine γ-lyase (CSE) contributes to oxidative stress in PCOS. The study also explored whether administration of sodium hydrosulfide (NaSH), an H2S donor, could ameliorate PCOS symptoms by reducing oxidative stress. The total eighteen rats were randomly assigned into three groups (n=6): control, PCOS, and PCOS+NaSH. PCOS was induced by intramuscular injection of estradiol valerate to induce PCOS in the PCOS and PCOS+NaSH groups. The PCOS+NaSH group received 30 μmol/L of NaSH in drinking water for 27 days after PCOS induction. Ovarian tissue samples were analyzed for oxidative stress indices including malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Additional analyses measured H2S levels, CBS, and CSE activity. PCOS induction led to a significant decrease in SOD activity, H2S levels, and CBS and CSE activity, accompanied by a significant increase in MDA levels (p<0.0001). Furthermore, PCOS caused severe histological alterations in the ovaries. However, administration of NaSH effectively restored all measured parameters to pre-PCOS induction levels (p<0.0001). This study showed that the decrease in the activity of H2S-producing enzymes and H2S levels may contribute to oxidative stress in PCOS. Therefore, administration of NaSH as a H2S donor can be considered as a potential therapeutic strategy for PCOS patients.

The effect of calorie-restriction along with thylakoid membranes of spinach on the gut-brain Axis Pathway and oxidative stress biomarkers in obese women with polycystic ovary syndrome: a Randomized, Double-blind, placebo-controlled clinical trial

BackgroundWomen with polycystic ovary syndrome (PCOS) have higher intestinal mucosal permeability, leading to the lipopolysaccharide (LPS) leakage and endotoxemia. This, in turn, leads to oxidative stress (OS) and neuro-inflammation caused by the gut-brain axis, affecting the neurotrophic factors levels such as brain-derived neurotrophic factor (BDNF) and S100 calcium-binding protein B (S100 B) levels. In this study, it was hypothesized that the thylakoid membranes of spinach supplementation along with a hypocaloric diet may have improved the LPS levels, neurotrophic factors, and OS in PCOS patients.MethodsIn this double-blind, randomized, placebo-controlled, and clinical trial, 48 women with obesity and diagnosed with PCOS based on Rotterdam criteria were randomly assigned to thylakoid (N = 21) and placebo groups (N = 23). A personalized hypocaloric diet with 500 calories less than the total energy expenditure was prescribed to all patients. The participants were daily supplemented with either a 5 g/day thylakoid-rich spinach extract or a placebo (5 g cornstarch) for 12 weeks along with a prescribed low-calorie diet. Anthropometric measurements and biochemical parameters were assessed at baseline and after the 12-week intervention.ResultsA statistically significant decrease in the LPS levels (P < 0.001) and an increase in the BDNF levels (P < 0.001) were recorded for the participants receiving the oral thylakoid supplements and a low-calorie diet. Furthermore, significant decreases were observed in fasting blood glucose, insulin, homeostatic model of assessment for insulin resistance, free testosterone index, and follicle-stimulating hormone / luteinizing hormone ratio in both groups (P < 0.05). No significant differences were detected between the two groups regarding the changes in malondialdehyde, catalase, total antioxidant capacity, and S100B levels (P > 0.05).ConclusionsIn sum, the thylakoid membranes of spinach supplemented with a hypocaloric diet reduced the LPS levels, increased the BDNF levels, and improved the glycemic profile and sex-hormone levels; however, they had no effects on the OS markers levels after 12 weeks of intervention.

Heavy Metals and Essential Elements in Association with Oxidative Stress in Women with Polycystic Ovary Syndrome-A Systematic Review.

Altered levels of heavy metals and essential elements have been associated with oxidative stress (OS) and metabolic and hormonal changes in women with polycystic ovary syndrome (PCOS). We aimed to summarize the knowledge on the association of heavy metals and essential elements with OS in PCOS. An electronic literature search using PubMed for studies published between January 2008 and April 2023 was conducted. We evaluated heavy metals and essential elements in relation to OS in PCOS in 15 articles. PCOS women had increased antimonium (Sb), cadmium (Cd), lead (Pb), mercury (Hg), arsenic (As), tellurium (Te), thallium (Tl) and osmium (Os) blood levels and decreased zinc (Zn) blood levels; the results of copper (Cu) blood levels were conflicting. Some studies showed a significant correlation between heavy metals (Sb, Cd, Pb, Hg, As, Te and Tl) and essential elements (Se, Zn, Cr, Ca, Mg and Cu) and markers of OS and chronic inflammation. Heavy metals (Sb, Cd, Pb and Hg) and essential elements (Zn, Cr, Se, Ca, Mg and Cu) were associated with metabolic and hormonal characteristics in PCOS. There might be a possible benefit from supplementation therapy in reducing OS and endocrinological problems related to PCOS. Our review confirmed an association between heavy metals and essential elements with OS in PCOS women. This systematic review is registered in PROSPERO under number CRD42023418453.

Could sestrin protein in serum be a new marker of oxidative stress in patients with polycystic ovary syndrome?

Objective PCOS (polycystic ovary syndrome) is one of the most common endocrinological disorders and it is the threshold of many systemic disorders. There are many studies in the literature on the mechanisms that cause increased oxidation in PCOS. Sestrin protein is known to regulate the oxidation. In this study, it is aimed to examine the changes in the level of sestrin protein in women with PCOS. Methods A total of 60 women participated the study, 30 of whom were diagnosed with PCOS according to the Rotterdam criteria. Also, 30 women were included in the study as the control group. Demographic information, biochemical analysis results, and sestrin levels of the patients in each group were compared. Results The median sestrin level was 6.2 ± 0.8 in the PCOS group and 3.38 ± 0.4 in the control group (p < 0.001). As a result of the evaluation made with ROC analysis, it is observed that serum sestrin levels may be meaningful in the diagnosis of polycystic ovary syndrome. The area under the curve (AUC) value for the 4.69 level was 99.4% (p < 0.001, 95% CI: 96.7% vs. 100%, sensitivity: 100%, specificity: 96.7%). Conclusions Sestrin protein is associated with oxidative stress. Sestrin protein can be used as an indicator of increased oxidative stress in PCOS.

Inter relationship of sympathetic reflex response and oxidative stress in polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is a very common reproductive endocrine disorder. Altered cardiovascular autonomic modulation and oxidative stress may predispose PCOS patients to cardiac events in the long term. Objective: To assess the relationship between sympathetic autonomic reactivity and oxidative stress in patients with polycystic ovary syndrome. Methods: This cross-sectional study was conducted in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka from September 2018 to August 2019 on 35 newly diagnosed obese (BMI ≥25kg/m2) PCOS patients aged 20-35 years. Age and BMI matched 35 apparently healthy subjects were also enrolled. Two noninvasive conventional autonomic function tests, such as systolic blood pressure (SBP) fall during active standing and diastolic blood pressure (DBP) rise during sustained handgrip were conducted on all subjects for evaluation of sympathetic reactivity. For assessment of oxidative stress, plasma malondialdehyde level as oxidant and plasma catalase level as antioxidant were measured in all subjects by spectrophotometry. For statistical analysis Independent sample “t” test, Pearson’s correlation test and multiple regression analysis were done. Results: In this study PCOS patients had significantly higher resting heart rate, SBP and DBP than healthy control (p&lt;0.01). Fall of SBP during standing was significantly lower (p&lt;0.05) while rise of DBP during sustained handgrip was significantly higher (p&lt;0.05) in PCOS compared to healthy control. Plasma catalase level was significantly lower (p&lt;0.01) and plasma malondialdehyde level significantly higher (p&lt;0.001) in PCOS in comparison to healthy control. On correlation analysis, rise of DBP showed significant negative correlation (p&lt;0.05) with plasma catalase level in PCOS. On multiple regression analysis rise of DBP showed significant negative (p&lt;0.01) association with plasma catalase and significant positive (p&lt;0.01) association plasma malondialdehyde in PCOS. Conclusion: Based on these results it is concluded that measures of sympathetic reactivity were related to oxidative stress in PCOS. J Bngladesh Soc Physiol 2021;16(1): 61-69

Assessment of the Parameters of Oxidative Stress Depending on the Metabolic and Anthropometric Status Indicators in Women with PCOS.

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in females of reproductive age. In women with PCOS, metabolic disorders such as insulin resistance (IR), hyperinsulinemia, obesity, diabetes mellitus, and other elements of metabolic syndrome are likely to occur. Studies have shown an increase in the concentration and activity of oxidative stress (OS) markers in patients with PCOS, compared to that in unaffected women. The aim of this study was to evaluate the parameters of OS in PCOS and their activity in relation to women without menstrual disorders with a normal body weight. Then, we compared malonodialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), including overweight and obesity, hyperandrogenemia, and IR in the PCOS group. The study included 35 women aged 18–46, hospitalized for menstrual disorders in the form of infrequent menstruation. In 26 women, PCOS was diagnosed on the basis of the Rotterdam Criteria; these patients qualified for the study group. The control group (n = 21) consisted of patients without menstrual disorders and without PCOS in an ultrasound examination. Patients were diagnosed between the 2nd and 5th day of the cycle. The parameters of OS were analyzed and compared with the anthropometric parameters and the lipid profile of the patients. Enzymatic activity of GPx, CAT, SOD, and MDA levels was determined in both groups. MDA levels and CAT activity differed significantly between the groups. There was a decrease in MDA levels in the IR group and the involvement of GPx in the excess weight and obesity and IR group accompanied by an increase in hip circumference. It therefore seems that IR may be the main risk factor to exposure to OS in patients with PCOS, independent from obesity. In addition, GPx is involved in every step in the development of the pathological condition in PCOS.

Indicator of early kidney injury in adolescents with polycystic ovary syndrome: Can urine NGAL level be?

Introduction and Purpose The Urinary Neutrophil-gelatinase associated lipocalin (NGAL) levels which are a biomarker for early diagnosis of kidney damage that may develop in patients with Polycystic Ovary Syndrome (PCOS) were investigated in the study. Material and Methods The 30 patients diagnosed with Polycystic Ovarian Syndrome between the ages of 13 and 18 who applied to the Yuzuncu Yil University General Children's Outpatient Clinic were included in the PCOS group and 30 healthy adolescents without any known acute or chronic illness and drug use were included in the control group. Findings Urine NGAL value was 842.204 ± 21.561 in PCOS group and 775.379 ± 23.98 in control group. NGAL level in PCOS group was statistically significantly higher than control group (p: .045). When we examine the relationship between dyslipidemia and PCOS; While dyslipidemia was positive in 10 (33.7%) patients in the PCOS group, it was negative in 20 (66.7%) patients. While 1 patient had dyslipidemia, 29 patients did not have dyslipidemia in the control group. A significant relationship was found between dyslipidemia and PCOS (p: .005). Conclusion We found that subclinical kidney dysfunction started in early stage patients in PCOS in our study. The urine NGAL level was thought to increase in response to increased oxidative stress in PCOS. We found no relationship between, insulin resistance and urea, BUN, creatinine and NGAL levels. However, we found a negative correlation between NGAL level and LDL. In addition, dyslipidemia, insulin resistance and ALT elevation were detected in the PCOS group.

Relationship between parasympathetic reactivity and oxidative stress in Polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is a very common reproductive hormone disorder. Altered cardiovagal autonomic modulation and oxidative stress may predispose PCOS patients to increased cardiovascular morbidity.&#x0D; Objective: To assess the relationship between parasympathetic reactivity and oxidative stress in patients with PCOS.&#x0D; Methods: This crosssectional study was conducted in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbagh, Dhaka from September 2018 to August 2019 on 35 newly diagnosed obese (BMI ≥25kg/m2) PCOS patients aged 20-35 years. Age and BMI matched 35 apparently healthy women were also enrolled as control. Three noninvasive conventional autonomic function tests, such as heart rate response to deep breathing, standing and the Valsalva maneuver, were used for evaluation of parasympathetic reactivity. For assessment of oxidative stress, plasma malondialdehyde level (oxidant) and plasma catalase level(antioxidant) were measured in all subjects by spectrophotometry. Data were expressed as mean± SD. For statistical analysis Independent sample “t” test, Pearson’s correlation test and multiple regression analysis were done as applicable.&#x0D; Results: In this study PCOS patients had significantly higher (p&lt;0.01)resting heart rate, systolic and diastolic blood pressure than that of healthy control. But Expiration: Inspiration ratio, Expiration:Inspiration difference and 30:15 ratio during standing were significantly lower (p&lt;0.001, p&lt;0.01 and p&lt;0.05 respectively) in PCOS compared to control. In addition, plasma catalase level was significantly lower (p&lt;0.01)and plasma malondialdehyde level significantly higher (p&lt;0.001) in PCOS in comparison to healthy control. Multiple regression analysis showed plasma catalase as a significant positive predictor (p&lt;0.05) of the Valsalva ratio in PCOS. Also, Valsalva ratio showed significant negative association (p&lt;0.05) with plasma malondialdehyde (p&lt;0.01)in PCOS.&#x0D; Conclusion: Based on these results it is concluded that impaired parasympathetic reactivity showed inverse relationship with oxidative stress in PCOS.&#x0D; J Bangladesh Soc Physiol. 2019, December; 14(2): 48-55

Oxidative Stress and Polycystic Ovary Syndrome: A Brief Review.

Polycystic ovary syndrome (PCOS) is one of the most common hormonal disorders, occurring in 5–10% women in reproductive ages. Despite a long history of studies on PCOS, its etiology is still unknown. Oxidative stress is now recognized to play a central role in the pathophysiology of many different disorders, including PCOS. Although intracellular reactive oxygen species (ROS) production and propagation are controlled by highly complex antioxidant enzymatic and non-enzymatic systems, understanding of mechanisms that oxidative stress is important to develop strategies for prevention and therapy of PCOS. This article reviews the literature data related to the mechanisms of oxidative stress in PCOS.

Elevated levels of the circulatory ischemia-modified albumin in patients with polycystic ovary syndrome: a meta-analysis

Oxidative stress (OS) has been reported to be associated with the pathogenesis of polycystic ovary syndrome (PCOS). Ischemia-modified albumin (IMA) levels in the circulation have been recently studied as a novel marker of OS. The studies in the literature on IMA levels in PCOS are inconsistent. This meta-analysis was conducted to compare circulatory IMA levels between PCOS patients and non-PCOS controls. Relevant studies were retrieved by online database and manual searching. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) were obtained by a random-effects meta-analysis. The funnel plot analysis with Begg’s and Egger’s tests was used for publication bias. A total of nine studies were included in this meta-analysis. The results indicated that the serum IMA levels were significantly elevated in PCOS patients as compared to non-PCOS controls (SMD = 0.49, 95% CI = 0.23–0.75, Z = 3.75, p = .0002). A one-study leave-out sensitivity analysis indicated that no single study had a significant influence on the overall outcome, suggesting the good validity and stability of these meta-analytic results. There was no evidence of publication bias as evidenced by the Egger (p = .28) and Begg’s tests (p = .21). The present meta-analysis suggests that IMA might be considered as a reliable and novel marker reflecting increased OS in PCOS.

Evaluation of pro-oxidant-antioxidant balance (PAB) and its association with inflammatory cytokines in polycystic ovary syndrome (PCOS)

Chronic low-grade inflammation has been suggested as a key contributor of the pathogenesis and development of polycystic ovary syndrome (PCOS). To investigate the association between oxidative stress status and inflammatory cytokines in follicular fluid of 21 PCOS women compared to 21 women with normal ovarian function who underwent intra-cytoplasmic sperm injection. Concentration of IL-6, IL-8, IL-10, and TNF-α was measured using sandwich ELISA. Oxidative stress was examined by measuring total oxidant status (TOS), malondialdehyde (MDA), total antioxidant capacity (TAC), and thiol groups. PCOS women had an elevated concentration of MDA and TOS compared to controls. Levels of TAC and thiol groups were lower in PCOS compared to controls. PCOS patients had a higher concentration of IL-6, IL-8, and TNF-α compared to controls. Concentration of IL-10 was lower in PCOS compared to controls. Significant correlations were found between MDA and TOS concentration with TNF-α and between IL-6 and MDA, IL-8 and TAC, IL-10 and TOS levels and also between IL-10 and TAC levels. TAC and thiol groups were negatively correlated with TNF-α. Increased oxidative stress in PCOS is associated with inflammation which is closely linked. Inflammation can induce production of inflammatory cytokines in this syndrome and directly stimulates excess ovarian androgen production.

Oxidative stress status in Chinese women with different clinical phenotypes of polycystic ovary syndrome.

To determine oxidative stress status and its association with clinical and metabolic parameters in Chinese women with different clinical phenotypes of polycystic ovary syndrome (PCOS). A cross-sectional study. A total of 544 patients with PCOS and 468 control women were included. The total oxidant status (TOS) was determined using a microplate colorimetric method. Total antioxidant capacity (T-AOC), oxidative stress index (OSI, the ratios of TOS to T-AOC) and clinical, hormonal and metabolic parameters were also analysed. TOS and OSI were significantly higher in each of the four PCOS phenotypes based on the Rotterdam criteria than in the control women and higher in patients with hyperandrogenism (HA) than in those without HA (P < 0·05). TOS, T-AOC and OSI were higher in lean patients than in lean controls (P < 0·05). These values, except OSI, were also higher in overweight/obese patients than in lean patients, and lean or overweight/obese controls (P < 0·05). Multivariate regression analysis demonstrated that apolipoprotein (apo)A1, the Ferriman-Gallwey score, triglyceride (TG), oestradiol (E2 ), high-density lipoprotein cholesterol (HDL-C) and 2-h glucose levels were the main predictors of TOS; the Ferriman-Gallwey score, E2 , apoA1, TG and HDL-C levels were the main predictors of OSI. Patients with PCOS with HA have higher oxidative stress levels compared with those without HA. The increased oxidative stress in PCOS is related to HA status, increased plasma glucose, TG, HDL-C and E2 levels, decreased apoA1 concentrations and a relative shortage of antioxidant capacity.

Up-regulation of miR-21 and 146a expression and increased DNA damage frequency in a mouse model of polycystic ovary syndrome (PCOS).

Introduction: Polycystic ovary syndrome (PCOS), a multigenic endocrine disorder, is highly associated with low-grade chronic inflammation, however its etiology remains unclear. In this study, we employed dehydroepiandrosterone (DHEA)-treated mice to reveal the molecular mechanism of inflammation and its correlation with oxidative stress in PCOS patients. Methods: miR-21 and miR-146a expression levels were measured using quantitative real-time polymerase chain reaction (qRT-PCR). DNA strand breakage frequency was measured using the single cell gel electrophoresis (SCGE) assay (comet assay) and micronucleus test (MN). CRP levels were measured by ELISA method and ESR values were measured by means of Micro-Dispette (Fisher No: 02-675-256) tubes according to the manufacturer’s instructions. Data were analyzed using one-way ANOVA in SPSS 21.0 software. Results: Our results showed that miR-21 and miR-146a as inflammation markers were upregulated in the sample group in comparison with control group. Erythrocyte sedimentation rate (ESR) and C- reactive protein (CRP) levels were also increased in mouse models of PCOS (p < 0.000). Micronucleated polychromatic erythrocyte (MNPCE) rates per 1000 polychromatic erythrocyte (PCE) significantly increased in DHEA treated mice (6.22 ± 3.28) in comparison with the controls (2.33 ± 2.23, p < 0.000). Moreover, mean arbitrary unit in DHEA treated animals (277 ± 92) was significantly higher than that in controls (184 ± 76, p = 0.005). Conclusion: To conclude, increased DNA strand breakage frequency and increased expression levels of miR-21 and miR-146a in DHEA administrated animals suggest that low grade chronic inflammation and oxidative stress can act as the main etiologies of PCOS.

Roles of Oxidative Stress in Polycystic Ovary Syndrome and Cancers

Oxidative stress (OS) has received extensive attention in the last two decades, because of the discovery that abnormal oxidation status was related to patients with chronic diseases, such as diabetes, cardiovascular, polycystic ovary syndrome (PCOS), cancer, and neurological diseases. OS is considered as a potential inducing factor in the pathogenesis of PCOS, which is one of the most common complex endocrine disorders and a leading cause of female infertility, affecting 4%–12% of women in the world, as OS has close interactions with PCOS characteristics, just as insulin resistance (IR), hyperandrogenemia, and chronic inflammation. It has also been shown that DNA mutations and alterations induced by OS are involved in cancer pathogenesis, tumor cell survival, proliferation, invasion, angiogenesis, and so on. Furthermore, recent studies show that the females with PCOS are reported to have an increasing risk of cancers. As a result, the more serious OS in PCOS is regarded as an important potential incentive for the increasing risk of cancers, and this study aims to analyze the possibility and potential pathogenic mechanism of the above process, providing insightful thoughts and evidences for preventing cancer potentially caused by PCOS in clinic.

Abdominal obesity can induce both systemic and follicular fluid oxidative stress independent from polycystic ovary syndrome

ObjectiveThe abdominal form of obesity is prevalent in women with polycystic ovary syndrome (PCOS). Visceral fat accumulation seems to play an important role in etiology of PCOS. In this cross-sectional study we evaluated the association of oxidative stress (OS) induced with PCOS and abdominal obesity in serum and follicular fluid (FF) of infertile women. Study designA total of 80 women younger than 37 years old undergoing an IVF program were studied in the same period of time from September 2012 to October 2013. Blood serum and FF obtained from 40 women with PCOS (diagnosed by the Rotterdam 2004 criteria) and 40 women without PCOS undergoing IVF were evaluated for two OS markers: lipid peroxide (LPO) and total antioxidant capacity (TAC), after puncture. The patients were divided into 4 groups on the basis of presence of PCOS and waist-to-hip ratio (WHR) or abdominal obesity (OA). ResultsHealthy and PCOS women with abdominal obesity had significantly higher amounts of LPO in the serum and FF as compared with women without abdominal obesity. LPO concentration in FF was significantly lower than in serum and corroborates the hypothesis that the germinal cells have a potent antioxidant mechanism. We also found that LPO concentration in the PCOS group associated with AO had an increasing trend vs. those AO patients without PCOS but this difference was not significant, so the increase in LPO level was approximately independent of PCOS. Based on our results, the association and interaction between PCOS and AO can lead to TAC concentration reduction in patients. ConclusionsAbdominal obesity can induce local and systemic oxidative stress in PCOS and non-PCOS patients. We suggest that PCOS-induced disorders are likely to be exacerbated in the presence of abdominal obesity.

Interleukin–33, Oxidative Stress in Prediabetic Polycystic Ovary Syndrome Patients with Insulin Resistance

Background: Polycystic ovary syndrome (PCOS) is one of the common female endocrine disorders of uncertain etiology, which causes menstrual disorders as well as infertility. Interleukin–33(IL-33) is considered as a strong risk marker of inflammation and may have possible role in pathogenesis of PCOS.Objectives: The present study is designed to investigate the possible role of IL-33 in pathogenesis of PCOS and its relation with glycated hemoglobin (HbA1C),insulin resistance(IR) and oxidative stress in prediabetic PCOS patients.Subjects and Methods: The study involved 30 healthy women as control group and sixty six infertile Iraqi women with PCOS which were divided into two groups according to glycated heamoglobin(HbA1c) value and homeostasis model assessment for insulin resistance (HOMA-IR). The first group (G1) consist of 30 women with HbA1c ≤ 6.5% and HOMA –IR&lt;3.8 as PCOS without diabetes and without insulin resistance. The second group(G2) consist of 36 patients with HbA1c ≥ 6.5 % and HOMA-IR ≥ 3.8 as PCOS with pre diabetes type 2 and insulin resistance. Ten milliliters of blood were collected from all subjects by vein puncture during 2nd – 4th day of the menstrual cycle. Two ml of blood were collected in EDTA tube for HbA1c analysis. The serum which obtained from the remained blood were used for determination of (insulin, fasting blood glucose(FBG), Malondialdehyde(MDA) , Total antioxidant capacity(TAC) , uric acid, glutathione(GSH), albumin, and IL-33) .Results: Results revealed a significant elevation in HbA1c, insulin, HOMA-IR, MDA, TAC, uric acid and IL-33 in the patients group when compared with healthy women. On the other hand, a significant decreased in GSH and albumin were found in patients group when compared with control group. Also there are significant differences in the results between patients in group 1 and group 2. A significant positive correlation between IL-33 and HbA1c levels was noticed in G1 and G2 .A significant positive correlation between IL-33 and HOMA-IR was noticed in group 1 while a negative significant correlation was found in group 2. No correlation founded between IL-33 levels and TAC concentration in group 1, but a positive correlation noticed with group 2. A significant negative correlation was observed between IL-33 and MDA/TAS ratio in G1, while a significant positive correlation in G2 was found.Conclusion: high levels of IL-33 in patient groups may be considered as a novel cytokine involved in the pathogenesis of PCOS. Also the elevation in oxidative stress in PCOS patients could be a reason for disturbed follicular development and ultimately infertility.

Superoxide dismutase in polycystic ovary syndrome patients undergoing intracytoplasmic sperm injection

Polycystic ovary syndrome (PCOS) is associated with oxidative stress (OS) and serum superoxide dismutase (SOD) activity has been reported with mixed results. The objective of this study was to examine the activity of SOD both in the serum and FF from women with PCOS undergoing ICSI, as well as the expression of Cu/Zn-SOD mRNA in the cells recovered from the FF. Forty women undergoing an ICSI trial were divided into: group I, included 20 PCOS cases, group II included 20 age-matched controls with tubal factor infertility. Both groups were similarly stimulated. A total of 204 metaphase II (MII) oocytes were aspirated; (108) from PCOS, and (96) from the control group. SOD activities in the serum and FF, as well as Cu/Zn-SOD (SOD1) mRNAs in follicular fluid (FF) cells were analyzed. There was a statistically highly significant decrease (p < 0.001) both in the mean serum SOD (45.56 ± 18.06) and FF SOD activity (42.49 ± 11.46) in PCOS than the control group (77.38 ± 7.82), (74.37 ± 6.15) respectively. The mean relative levels of Cu, Zn SOD mRNAs was significantly lower (p < 0.001) in cells isolated from the FF in PCOS (0.36 ± 0.14) than the control group (0.81 ± 0.15). SOD activity in FF had no effects on fertilization rate (p > 0.05), or embryo quality after intracytoplasmic sperm injection (ICSI). Although decreased SOD activity in FF has no effect on fertilization rate and/or embryo quality, serum SOD activity could be a clinical parameter for determining systemic oxidative stress in PCOS.