Induction of Hyperandrogenism in Lean Reproductive-Age Women Stimulates Proatherogenic Inflammation

González, Fidelina; Nair, K. Sreekumaran; Basal, Eati; Bearson, Dawn M.; Schimke, Jill M.; Blair, Hilary

doi:10.1055/s-0034-1387791

Cited by 7 publications

(5 citation statements)

References 37 publications

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“…Which was in line with Dehdashtihaghighat et al, [43] who observed increased CRP in case of PCOS and they reported that this increase could be due to excess production in the liver under the influence of interleukin-6 and TNF-a , but it was independent on BMI or IR and it could be due to hyperandrogenism in those patients, also, as reported by Gonzalez et al, [54] that is in lean reproductive age women, proatherognic and inflammatory markers increased after raising circulating androgens to levels observed in PCOS. However, the definite cause of CRP increase in PCOS is unknown.…”

Section: Discussionsupporting

confidence: 89%

Effect of Selinum on Ovarian Structure, Function and Serum Osteopontin Level in Rat Model of Polycystic Ovary Syndrome

Khalil¹,

El-Malkey²,

Aref³

et al. 2018

The Medical Journal of Cairo University

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Background: Selenium supplementation could be effective on reproductive function, however, its effect on serum Osteopontin (OPN) level in Polycystic Ovary Syndrome (PCOS) is not studied yet. Aim of Work:The present study examines the effect of selinum on ovarian structure and function, in addition to its effect on OPN level in letrozole-induced PCO rat model. Material and Methods:Thirty albino rats were included in the study and divided into 3 groups: Group (I): Normal control group, Group (II) PCOS group and Group (III): PCOS treated group with intra peritoneal (i.p.) sodium selenite (0.3 mg/kg) for 14 days after PCO induction, which was induced by oral letrozol (1mg/kg) daily for 21 consecutive days. At the end of the experiment physical parameters (body weight, duration of oestrous cycle, ovarian and uterine weights) were estimated, metabolic parameters (glucose, insulin and calculated HOMA-IR), hormonal profile (total testosterone, 17 pestradiol, progesterone, FSH and LH), inflammatory mediators (OPN and C-Reactive Protein (CRP)), and finally macro anatomical and micro morphological studies of the ovaries were done.Results: There was a significant increase in serum FSH, LH, testosterone, CRP, OPN, body weight and duration of esterous cycle with significant decrease in estradiol, progesterone level and uterine weight accompanied by appearance of multiple ovarian cysts and disappearance of corpus luteum in histological studies in Group II. However, selinum treatment for fourteen days reversed the above mentioned findings except for body weight. Moreover, OPN showed a significant positive correlation with FSH, LH and CRP. While it showed a significant negative correlation with estradiol and progesterone in both Group II and III.Conclusion: Treatment with selinum exerts beneficial effects in PCOS rats which might be due to its antiinflammatory properties.

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Section: Discussionsupporting

confidence: 89%

Effect of Selinum on Ovarian Structure, Function and Serum Osteopontin Level in Rat Model of Polycystic Ovary Syndrome

Khalil¹,

El-Malkey²,

Aref³

et al. 2018

The Medical Journal of Cairo University

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“…In the present study, OS was augmented in the L group, and it was evidenced by the increased level of MDA and the decreased level of antioxidants in ovarian tissues. Lipid peroxidation may result from excess proinflammatory cytokine production, as evidenced by decreased serum TNF‐α in the present study (Gonzalez et al, ) or IR‐induced hyperglycemia (Ullah et al, ).…”

Section: Discussionmentioning

confidence: 47%

“…Excess androgen also can arrest follicular development indirectly via OS and proinflammatory cytokines, which enhance apoptosis in granulosa cells resulting in bad oocyte quality and finally progressive atresia of ovarian follicles (Rezvanfar et al, ). Excess testosterone could increase nuclear factor kappa B (NF‐κB) gene expression and proinflammatory gene expression and stimulate circulating mononuclear cells (Gonzalez et al, ). This was confirmed in the present study by the increased serum TNF‐α in the L group, and this is compatible with the study of Salmabadi, Mohseni Kouchesfahani, Parivar, & Karimzadeh ().…”

Section: Discussionmentioning

confidence: 99%

Pathophysiological changes in experimental polycystic ovary syndrome in female albino rats: Using either hemin or L‐arginine

Ragy

Abdel-Hamid

Toni

2018

Journal Cellular Physiology

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Polycystic ovary syndrome (PCOS), one of the important endocrine disorders affecting females in the reproductive age, is caused mainly by an abnormal oxidation status that subsequently causes inflammatory conditions. Thus, this study aims to examine the possible individual prophylactic effects of gasotransmitters, hemin, or L‐arginine in letrozole‐induced PCOS. Fifty adult female albino rats were used and separated into a control group, which received the vehicle; a letrozole‐induced PCOS group (L), which received letrozole orally at a dose level of 1 mg/kg for 21 days; a letrozole+hemin (L+H) group, which received letrozole plus hemin at a dose level of 25 mg/kg injected IP twice per week for 21 days; and a letrozole+L‐arginine (L+A) group, which received letrozole plus L‐arginine at a dose level of 200 mg/kg orally for 21 days. During PCO induction, the body weight and Lee index were measured. Serum glucose, insulin, lipid profile, gonadotrophic hormones, testosterone, estrogen, and tumor necrosis factor alpha were assayed, while ovarian tissues were analyzed to measure the oxidative state and histopathological changes. Our results proved that either hemin or L‐arginine administration could improve the oxidative state, the inflammatory reaction, the hormonal imbalance, and the metabolic disturbances in PCO rats, which was confirmed by a histopathological examination of the rats’ ovaries. In conclusion, either hemin or L‐arginine had protective effects against PCOS with better pathophysiological changes with hemin.

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“…Inflammation in lean women with PCOS could have other pathogenic mechanisms, but most studies of parameters of chronic low-grade inflammation have been conducted in overweight or obese patients with PCOS. A study of healthy, lean women without PCOS treated with dehydroepiandrosterone sulfate (DHEA-S) showed an increase in inflammatory parameters after an increase in androgen levels [35]. Thus, it can be suggested that the cause of chronic low-grade inflammation in lean patients is hyperandrogenemia.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory and Anti-Inflammatory Parameters in PCOS Patients Depending on Body Mass Index: A Case-Control Study

Vasyukova,

Zaikova,

Kalinina

et al. 2023

Biomedicines

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Background: it has been suggested that chronic low-grade inflammation plays an important role in the pathogenesis of polycystic ovary syndrome (PCOS). According to previous studies, it remains unclear which cytokines influence the development of this syndrome and whether their increase is associated with the presence of excess weight/obesity or is an independent factor. The aim of our research was to determine the parameters of chronic inflammation in women with PCOS in comparison with healthy women in the normal weight and the overweight subgroups. Methods: This case-control study included 44 patients with PCOS (19 women with a body mass index (BMI) < 25 kg/m² and 25 women with a BMI ≥ 25 kg/m²) and 45 women without symptoms of PCOS (22 women with a BMI < 25 kg/m² and 23 women with a BMI ≥ 25 kg/m²). Thirty-two cytokines were analyzed in the plasma of the participants using Immunology multiplex assay HCYTA-60K-PX48 (Merck Life Science, LLC, Germany). Results: Cytokines: interleukin-1 receptor antagonist (IL-1 RA), IL-2, IL-6, IL-17 E, IL-17 A, IL-18, and macrophage inflammatory protein-1 alpha (MIP-1 α) were increased in women with PCOS compared to controls, both in lean and overweight/obese subgroups (p < 0.05). Moreover, only lean women with PCOS had higher levels of IL-1 alpha, IL-4, IL-9, IL-12, IL-13, IL-15, tumor necrosis factor (TNF- α) alpha and beta, soluble CD40 and its ligand (SCD40L), fractalkine (FKN), monocyte-chemotactic protein 3 (MCP-3), and MIP-1 β compared to the control group (p < 0.05). IL-22 was increased in the combined group of women with PCOS (lean and overweight/obese) compared to the control group (p = 0.012). Conclusion: Chronic low-grade inflammation is an independent factor affecting the occurrence of PCOS and does not depend on the presence of excess weight/obesity. For the first time, we obtained data on the increase in such inflammatory parameters as IL-9, MCP-3, and MIP-1α in women with PCOS.

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Induction of Hyperandrogenism in Lean Reproductive-Age Women Stimulates Proatherogenic Inflammation

Cited by 7 publications

References 37 publications

Effect of Selinum on Ovarian Structure, Function and Serum Osteopontin Level in Rat Model of Polycystic Ovary Syndrome

Effect of Selinum on Ovarian Structure, Function and Serum Osteopontin Level in Rat Model of Polycystic Ovary Syndrome

Pathophysiological changes in experimental polycystic ovary syndrome in female albino rats: Using either hemin or L‐arginine

Inflammatory and Anti-Inflammatory Parameters in PCOS Patients Depending on Body Mass Index: A Case-Control Study

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