Inter‐related effects of insulin resistance, hyperandrogenism, sympathetic dysfunction and chronic inflammation in <scp>PCOS</scp>

Shorakae, Soulmaz; Ranasinha, Sanjeeva; Abell, Sally K.; Lambert, Gavin W.; Lambert, Elisabeth; Courten, Barbora de; Teede, Helena

doi:10.1111/cen.13808

Cited by 119 publications

(83 citation statements)

References 53 publications

(125 reference statements)

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“…chronic inflammation plays an important role in the development of PcoS (31,32). The Tlr4/nF-κB pathway has distinct functions during the stress reaction and inflammation (33).…”

Section: Discussionmentioning

confidence: 99%

Cryptotanshinone alleviates polycystic ovary syndrome in rats by regulating the HMGB1/TLR4/NF‑κB signaling pathway

Yang

Cao

et al. 2020

Mol Med Rep

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cryptotanshinone (crY) has been demonstrated to reverse reproductive disorders. However, whether crY is effective in the treatment of polycystic ovary syndrome (PcoS) remains unknown. The aim of the present study was to evaluate the therapeutic potential of crY in PcoS. a rat model of PcoS was established by daily injection of human chorionic gonadotropin and insulin for 22 days. Total body weight and ovarian weight, as well as the levels of luteinizing hormone (lH) and the lH to follicle-stimulating hormone (FSH) ratio (LH/FSH) significantly increased in rats with PCOS, compared with controls. Moreover, the levels of testosterone (T), tumor necrosis factor (TnF)-α and high-mobility group box 1 protein (HMGB1) also increased. However, crY treatment attenuated the increase in body weight, ovarian weight, lH, lH/FSH ratio, T, TnF-α and HMGB1 levels, compared with the PcoS group. Treatment with crY also reduced NF-κB/p65, HMGB1 and toll-like receptor (TLR)4 mrna and protein expression levels in the ovarian tissue and granulosa cells, both in vitro and in vivo. Thus, CRY significantly mitigated the changes in body weight, ovary weight, hormone levels and inflammatory factor levels observed in rats with PcoS. Thus, crY protects against PcoS-induced damage of ovarian tissue, possibly through a regulatory pathway involving HMGB1, Tlr4 and nF-κB.

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“…chronic inflammation plays an important role in the development of PcoS (31,32). The Tlr4/nF-κB pathway has distinct functions during the stress reaction and inflammation (33).…”

Section: Discussionmentioning

confidence: 99%

Cryptotanshinone alleviates polycystic ovary syndrome in rats by regulating the HMGB1/TLR4/NF‑κB signaling pathway

Yang

Cao

et al. 2020

Mol Med Rep

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“…A recent study addressed the inter-related effects of insulin resistance, hyperandrogenism, chronic inflammation and sympathetic dysfunction (evaluated by MSNA) in 49 PCOS and 23 control women; based on the findings, the authors concluded that sympathetic dysfunction and hyperandrogenism were associated with PCOS and that chronic inflammation might be the mediating factor between sympathetic function, hyperandrogenism and insulin resistance 35. However, in the present study, the surrogate marker of sympathetic activity, LF SBP , did not significantly differ between the PCOS and control women, suggesting that in our population the women with PCOS would not have increased sympathetic activity.…”

Section: Discussionmentioning

confidence: 99%

Effect of polycystic ovary syndrome on cardiac autonomic function at a late fertile age: a prospective Northern Finland Birth Cohort 1966 study

et al. 2019

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ObjectivesPrevious studies of women in their 20s and 30s have reported impaired autonomic function in women with polycystic ovary syndrome (PCOS). We aimed to study, for the first time, whether PCOS is associated with impaired cardiac autonomic function independent of metabolic and hormonal status in their late reproductive years.DesignA prospective Northern Finland Birth Cohort 1966 (NFBC1966) study including 5889 women born in 1966 and followed through the age of 46. At that age, n=3706/5123 women (72%) answered the postal questionnaires and n=3280/5123 women (64%) participated in the clinical examination.SettingGeneral community.ParticipantsThe sample included women presenting both irregular menses (oligomenorrhoea or amenorrhoea) and hirsutism at age 31 (n=125) or with formally diagnosed PCOS by age 46 (n=181) and women without PCOS symptoms or diagnosis (n=1577).Primary and secondary outcome measuresHeart rate variability parameters: the root mean square of successive R-R differences (rMSSD), spectral power densities (LF: low frequency and HF: high frequency) and baroreflex sensitivity (BRS).ResultsWe found that parasympathetic activity (assessed by rMSSD: 19.5 (12.4; 31.9) vs 24.3 (16.1; 34.8) ms, p=0.004 and HF: 172 (75; 399) vs 261 (112; 565) ms2, p=0.002) and BRS (6.13±3.12 vs 6.99±3.52 ms/mm Hg, p=0.036) were lower in women with PCOS compared with the controls. However, in the multivariate regression analysis, PCOS, body mass index and the free androgen index did not significantly associate with rMSSD, whereas blood pressure, insulin resistance and triglycerides did.ConclusionsWe report here for the first time that late reproductive-aged women with PCOS display impaired cardiac autonomic function manifested as decreased vagal activity. Metabolic status, rather than hyperandrogenaemia and PCOS per se, was the strongest contributing factor. Given the link between cardiac morbidity and impaired autonomic function, the findings underline the importance of screening and treating metabolic abnormalities early on in women with PCOS.

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“…However, reported that alterations in DNA methylation profiles of the peripheral blood from women with PCOS corroborate those obtained from the ovary tissue, indicating that certain alterations in DNA methylation should be inferred from the peripheral blood, which is of great significance, as this would avoid the invasive procedure of the biopsy. Remarkably, all studies examining the peripheral blood indicate that the PCOS phenotype correlates with an alteration in the DNA methylation content of genes involved in the inflammatory response, glucose and lipid metabolism and hormone signaling, which, in turn, is associated with the presence of a systemic dysfunction characterized by chronic inflammation accompanied by hyperandrogenism and insulin resistance (Shorakae et al 2018). Besides, these alterations in the DNA methylation program could be acquired during fetal development as proposed by Lambertini et al (2017).…”

Section: R32mentioning

confidence: 97%

DNA methylation in the pathogenesis of polycystic ovary syndrome

et al. 2019

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Polycystic ovary syndrome (PCOS) is the leading endocrine and metabolic disorder in premenopausal women characterized by hyperandrogenism and abnormal development of ovarian follicles. To date, the PCOS etiology remains unclear and has been related to insulin resistance, obesity, type 2 diabetes mellitus, cardiovascular disease and infertility, among other morbidities. Substantial evidence illustrates the impact of genetic, intrauterine and environmental factors on the PCOS etiology. Lately, epigenetic factors have garnered considerable attention in the pathogenesis of PCOS considering that changes in the content of DNA methylation, histone acetylation and noncoding RNAs have been reported in various tissues of women with this disease. DNA methylation is changed in the peripheral and umbilical cord blood, as well as in ovarian and adipose tissue of women with PCOS, suggesting the involvement of this epigenetic modification in the pathogenesis of the disease. Perhaps, these defects in DNA methylation promote the deregulation of genes involved in inflammation, hormone synthesis and signaling and glucose and lipid metabolism. Research on the role of DNA methylation in the pathogenesis of PCOS is just beginning, and several issues await investigation. This review aims to provide an overview of current research focused on DNA methylation and PCOS, as well as discuss the perspectives regarding this topic.

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Inter‐related effects of insulin resistance, hyperandrogenism, sympathetic dysfunction and chronic inflammation in PCOS

Abstract: Sympathetic dysfunction and hyperandrogenism are significantly associated with PCOS. Chronic low-grade inflammation potentially mediates the effect of sympathetic dysfunction on hyperandrogenism and insulin resistance.

Cited by 119 publications

References 53 publications

Cryptotanshinone alleviates polycystic ovary syndrome in rats by regulating the HMGB1/TLR4/NF‑κB signaling pathway

Cryptotanshinone alleviates polycystic ovary syndrome in rats by regulating the HMGB1/TLR4/NF‑κB signaling pathway

Effect of polycystic ovary syndrome on cardiac autonomic function at a late fertile age: a prospective Northern Finland Birth Cohort 1966 study

DNA methylation in the pathogenesis of polycystic ovary syndrome

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