scholarly journals Cangfudaotan Decoction Alleviates Insulin Resistance and Improves Follicular Development in Rats with Polycystic Ovary Syndrome via IGF-1-PI3K/Akt-Bax/Bcl-2 Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Chenye Wang ◽  
Caifei Ding ◽  
Zhoujia Hua ◽  
Chunyue Chen ◽  
Jia Yu

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder prevalent in females of reproductive age; insulin resistance (IR) is the major pathogenic driver. Pharmacology is a basic option for PCOS therapy; traditional Chinese medicine (TCM), as a significant part of complementary and alternative medicine, has a long history in the clinical management of PCOS. Cangfudaotan decoction (CFD) has been used clinically for gynaecological diseases especially PCOS. In this study, first, chemical components in CFD were clarified using UPLC-Q/TOF-MS analysis. Then, an animal model of PCOS was established, granular cells were also isolated from the rats with PCOS, and CFD was administrated at different dosages in PCOS rats and granular cells, to investigate the therapeutic effect and mechanisms of CFD for PCOS treatment. The result showed that CFD treatment is effective in PCOS rats and granulosa cells. CFD was able to improve IR, restore the serum hormone levels, inhibit the inflammatory cytokines in PCOS rat, and alleviate ovary morphological injury and apoptosis in PCOS rats. In granulosa cells of PCOS, the result showed that the cell viability was improved, and cell apoptosis was inhibited after CFD administration. Further experiments suggested that CDF improves IR, follicular development, cell apoptosis, and inflammatory microenvironment, and this was associated to the regulation of IGF-1-PI3K/Akt-Bax/Bcl-2 pathway-mediated gene expression. Given that CFD sufficiently suppresses insulin resistance and improves follicular development in this study, exploring these mechanisms might help to optimize the therapeutic treatment of CFD in PCOS patients.

Reproduction ◽  
2018 ◽  
Vol 155 (5) ◽  
pp. R199-R209 ◽  
Author(s):  
Mariana Di Pietro ◽  
Natalia Pascuali ◽  
Fernanda Parborell ◽  
Dalhia Abramovich

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine pathology among women in reproductive age. Its main symptoms are oligo or amenorrhea, hyperandrogenism and the presence of ovarian cysts. It is also associated with infertility, obesity and insulin resistance. Mainly due to its heterogeneity, PCOS treatments are directed to manage its symptoms and to prevent associated diseases. The correct formation and regression of blood vessels during each ovarian cycle is indispensable for proper follicular development, ovulation and corpus luteum formation. The importance of these processes opened a new and promising field: ovarian angiogenesis. Vascular alterations characterize numerous pathologies, either with increased, decreased or abnormal angiogenesis. In the last years, several anomalies of ovarian angiogenesis have been described in women with PCOS. Therefore, it has been suggested that these alterations may be associated with the decreased – or lack of – ovulation rates and for the formation of cysts in the PCOS ovaries. Restoration of a proper vessel formation in the ovaries may lead to improved follicular development and ovulation in these patients. In the present review, we attempt to summarize the alterations in ovarian angiogenesis that have been described in women with PCOS. We also discuss the therapeutic approaches aimed to correct these alterations and their beneficial effects on the treatment of infertility in PCOS.


2020 ◽  
Vol 16 ◽  
Author(s):  
Antonio Schiattarella ◽  
Gaetano Riemma ◽  
Marco La Verde ◽  
Gianluigi Franci ◽  
Annalisa Chianese ◽  
...  

: Polycystic ovary syndrome (PCOS) is a condition that affects about 15% of women of reproductive age and is correlated with infertility, insulin resistance, and obesity. The etiology of PCOS is multifactorial and genetic, endocrine, and metabolic causes were involved. New evidence suggests a link between microorganisms residing in the digestive tracts of humans and the development of PCOS. Moreover, an imbalance in the gut microbial community could be a possible factor for the onset of insulin resistance and obesity. Hyperandrogenism, a key feature of PCOS, could also play a critical role in shaping the microbiome community. Probiotics could modify the gut microbiota and serve as a potential treatment for PCOS. Here we disclose the association between PCOS and intestinal microbiota and the possible role of probiotics as a new treatment approach.


Author(s):  
Sophie Catteau-Jonard ◽  
Cécile Gallo ◽  
Didier Didier

The polycystic ovary syndrome (PCOS) is the most common cause of anovulation and hyperandrogenism in women, affecting between 5 and 10% of women of reproductive age worldwide (1). Although this difficult topic in endocrine gynaecology is under extensive research, controversies still remain about the pathophysiology, diagnosis, and therapy of PCOS. The PCOS phenotype can be structured in three components: manifestations of anovulation, hyperandrogenism, and the metabolic syndrome (of which hyperinsulinaemia secondary to insulin resistance is the central abnormality). The latter two are addressed in other chapters. Our knowledge about the mechanism of disturbed folliculogenesis in PCOS that is responsible for its reproductive aspects has much increased these last years, thus opening new avenues for the diagnostic and therapeutic approaches.


2020 ◽  
Vol 11 ◽  
pp. 204201882093830 ◽  
Author(s):  
Mohammed Altigani Abdalla ◽  
Harshal Deshmukh ◽  
Stephen Atkin ◽  
Thozhukat Sathyapalan

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. Metabolic sequelae associated with PCOS range from insulin resistance to type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Insulin resistance plays a significant role in the pathophysiology of PCOS and it is a reliable marker for cardiometabolic risk. Although insulin sensitising agents such as metformin have been traditionally used for managing metabolic aspects of PCOS, their efficacy is low in terms of weight reduction and cardiovascular risk reduction compared with newer agents such as incretin mimetics and SGLT2 inhibitors. With current pharmaceutical advances, potential therapeutic options have increased, giving patients and clinicians more choices. Incretin mimetics are a promising therapy with a unique metabolic target that could be used widely in the management of PCOS. Likewise, bariatric procedures have become less invasive and result in effective weight loss and the reversal of metabolic morbidities in some patients. Therefore, surgical treatment targeting weight loss becomes increasingly common in the management of obese women with PCOS. Newer emerging therapies, including twincretins, triple GLP-1 agonists, glucagon receptor antagonists and imeglemin, are promising therapeutic options for treating T2DM. Given the similarity of metabolic and pathological features between PCOS and T2DM and the variety of therapeutic options, there is the potential to widen our strategy for treating metabolic disorders in PCOS in parallel with current therapeutic advances. The review was conducted in line with the recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome 2018.


2021 ◽  
Vol 47 (3) ◽  
pp. 130-149
Author(s):  
Joanna Smyczyńska

Polycystic ovary syndrome (PCOS) is one of the most common hormonal disorders and causes of infertility in women in reproductive age. Diagnostic criteria of PCOS in adult women include: ovulation disorders, hyperandrogenism and  polycystic ovaries. According to most recommendations, 2 out of these 3 criteria are confirm the diagnosis of PCOS. In girls during puberty and in the first years after menarche, different diagnostic criteria of menstrual disorders should be taken into account (variable length of menstrual cycles, monophasic cycles) and the limited usefulness of ultrasound examination for PCOS diagnosis within 8 years after menarche. Fairly extensive differential diagnosis is also necessary, especially – exclusion of adrenal hyperandrogenism. Moreover, the diagnostic criteria of PCOS do not take into account the metabolic disorders found in most patients (obesity, insulin resistance, type 2 diabetes), which should be diagnosed as early as possible and treated appropriately. This is especially true for teenagers, in whom the unequivocal diagnosis of PCOS or its exclusion may be very difficult. Current recommendations regard hormonal contraception as the first-line therapy in PCOS, in both adult women and adolescents. Together with its beneficial effect on the reduction of hyperandrogenism and obtaining regular bleeding (which in fact are not menstruations), the unfavorable metabolic effects of hormonal contraception are emphasized, as well as the inadequacy of its use if it is expected to achieve or restore ovulation and fertility. The latest reports indicate the legitimacy of treatment aimed at correcting disorders of carbohydrate metabolism and its greater effectiveness compared to the use of oral contraceptives in both adult women and girls with PCOS. In the pharmacotherapy of insulin resistance, metformin is of fundamental importance, the use of pioglitazone, GLP-1 receptor agonists or inositols is also proposed. Adequate lifestyle and dietary modification are of major importance in the treatment and prevention of PCOS. The mechanisms of "inheritance" of PCOS and insulin resistance with the participation of epigenetic modifications are still better understood, taking into account the effects of exposure to androgen excess in utero, intrauterine growth retardation, and maternal obesity and hyperalimentation. This creates new possibilities for PCOS prophylaxis.


Author(s):  
Chelsae Kuntal ◽  
Jyotsna Vyas ◽  
Asha Chaudhary ◽  
Sunita Hemani ◽  
Lata Rajoria

Background: Polycystic ovary syndrome is a common endocrinopathy in women of reproductive age with prevalence of 6-10% which is characterized by hyper androgenic features and chronic oligo – anovulation and polycystic ovary morphology. Most women with polycystic ovary syndrome are also characterized by metabolic abnormalities like insulin resistance, hyperinsulinemia, dyslipidemia and abdominal obesity, these forming risk factors for metabolic syndrome. The objective of the study was to compare the clinical, biochemical and hormonal profile of polycystic ovary syndrome patients with and without metabolic syndrome.Methods: A comparative cross- sectional study was undertaken on 79 PCOS women diagnosed with PCOS according to Rotterdam criteria, in which the clinical data and hormonal profile of two groups of polycystic ovary syndrome women with and without metabolic syndrome was compared.Results: The mean age of 79 patients in this study group with and without metabolic syndrome was 26.17±3.18 and 25.57±3.41 years respectively. There were more patients from urban areas as compared to rural areas and maximum patients. Significantly higher number of PCOS women with metabolic syndrome had hirsutism and acanthosis nigricans than those without metabolic syndrome. Mean value of Waist circumference, systolic BP pressure, diastolic BP, S. Triglyceride and fasting glucose were higher and HDL levels were lower in women with metabolic syndrome than those without metabolic syndrome. Fasting insulin and HOMA-IR values were significantly higher in PCOS women with metabolic syndrome in comparison to those without metabolic syndrome.Conclusion: PCOS is not only is the most frequent cause of anovulation, but it is also associated with characteristic metabolic disturbances that may have important implications for the long term health. Metabolic syndrome is a cluster of endocrine disturbances, including insulin resistance, dyslipidemia, obesity, and hypertension. It is associated with a two-fold increased risk of cardiovascular disease and a five-fold increased risk of type 2 diabetes. This illustrates the importance of early detection of insulin resistance and metabolic syndrome with subsequent application of preventive measures in women with polycystic ovary syndrome.


Author(s):  
Susan Sam

AbstractPolycystic ovary syndrome (PCOS) is the most common hormonal disorder among reproductive-age women and is associated with a high risk for metabolic disorders. Adiposity and insulin resistance are two prevalent conditions in PCOS and the likely culprits for the heightened metabolic risk. Up to 60% of women with PCOS are considered to be overweight or obese, and even among non-obese women with PCOS there is an increased accumulation of adipose tissue in abdominal depots. Insulin resistance in PCOS is unique and independent of obesity, as even non-obese women with this condition are frequently insulin resistant. However, obesity substantially aggravates the insulin resistance and the metabolic and reproductive abnormalities in women with PCOS. Recently, it has been shown that many aspects of adipose tissue function in PCOS are abnormal, and these abnormalities likely predispose to development of insulin resistance even in the absence of obesity. This review provides an overview of these abnormalities and their impact on development of metabolic disorders. At the end, an overview of the therapeutic options for management of adiposity and its complications in PCOS are discussed.


2015 ◽  
Vol 308 (12) ◽  
pp. E1076-E1084 ◽  
Author(s):  
Ilana B. Ressler ◽  
Bernadette E. Grayson ◽  
Yvonne M. Ulrich-Lai ◽  
Randy J. Seeley

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age. Although a comorbidity of PCOS is obesity, many are lean. We hypothesized that increased saturated fat consumption and obesity would exacerbate metabolic and stress indices in a rodent model of PCOS. Female rats were implanted with the nonaromatizable androgen dihydrotestosterone (DHT) or placebo pellets prior to puberty. Half of each group was maintained ad libitum on either a high-fat diet (HFD; 40% butter fat calories) or nutrient-matched low-fat diet (LFD). Irrespective of diet, DHT-treated animals gained more body weight, had irregular cycles, and were glucose intolerant compared with controls on both diets. HFD/DHT animals had the highest levels of fat mass and insulin resistance. DHT animals demonstrated increased anxiety-related behavior in the elevated plus maze by decreased distance traveled and time in the open arms. HFD consumption increased immobility during the forced-swim test. DHT treatment suppressed diurnal corticosterone measurements in both diet groups. In parallel, DHT treatment significantly dampened stress responsivity to a mild stressor. Brains of DHT animals showed attenuated c-Fos activation in the ventromedial hypothalamus and arcuate nucleus; irrespective of DHT-treatment, however, all HFD animals had elevated hypothalamic paraventricular nucleus c-Fos activation. Whereas hyperandrogenism drives overall body weight gain, glucose intolerance, anxiety behaviors, and stress responsivity, HFD consumption exacerbates the effect of androgens on adiposity, insulin resistance, and depressive behaviors.


2021 ◽  
Vol 12 ◽  
Author(s):  
Rusong Zhao ◽  
Yonghui Jiang ◽  
Shigang Zhao ◽  
Han Zhao

Polycystic ovary syndrome (PCOS) is the most common complex endocrine and metabolic disease in women of reproductive age. It is characterized by anovulatory infertility, hormone disorders, and polycystic ovarian morphology. Regarding the importance of granulosa cells (GCs) in the pathogenesis of PCOS, few studies have investigated the etiology at a single “omics” level, such as with an mRNA expression array or methylation profiling assay, but this can provide only limited insights into the biological mechanisms. Here, genome-wide DNA methylation together with lncRNA-miRNA-mRNA profiles were simultaneously detected in GCs of PCOS cases and controls. A total of 3579 lncRNAs, 49 miRNAs, 669 mRNAs, and 890 differentially methylated regions (DMR)-associated genes were differentially expressed between PCOS cases and controls. Pathway analysis indicated that these differentially expressed genes were commonly associated with steroid biosynthesis and metabolism-related signaling, such as glycolysis/gluconeogenesis. In addition, we constructed ceRNA networks and identified some known ceRNA axes, such as lncRNAs-miR-628-5p-CYP11A1/HSD17B7. We also identified many new ceRNA axes, such as lncRNAs-miR-483-5p-GOT2. Interestingly, most ceRNA axes were also closely related to steroid biosynthesis and metabolic pathways. These findings suggest that it is important to systematically consider the role of reproductive and metabolic genes in the pathogenesis of PCOS.


Author(s):  
Lihua Sun ◽  
Hui Tian ◽  
Songguo Xue ◽  
Hongjuan Ye ◽  
Xue Xue ◽  
...  

Polycystic ovary syndrome (PCOS) is an endocrinopathy with complex pathophysiology that is a common cause of anovulatory infertility in women. Although the disruption of circadian rhythms is indicated in PCOS, the role of the clock in the etiology of these pathologies has yet to be appreciated. The nuclear receptors REV-ERBα and REV-ERBβ are core modulators of the circadian clock and participate in the regulation of a diverse set of biological functions. However, in PCOS, the expression of REV-ERBs and their effects remain unclear. Here, we demonstrate that the levels of REV-ERBα and REV-ERBβ expression were lower in the granulosa cells of PCOS patients than in control subjects. In vitro, we found that the overexpression of REV-ERBα and REV-ERBβ, and their agonist SR9009, promoted the expression of mitochondrial biosynthesis genes PGC-1α, NRF1, and TFAM and inhibited autophagy in KGN cells. Our results also indicate that REV-ERBα and REV-ERBβ can inhibit apoptosis in granulosa cells and promote proliferation. Importantly, the REV-ERB agonist SR9009 ameliorates abnormal follicular development by promoting mitochondrial biosynthesis and inhibiting autophagy in a mouse PCOS model. This allows us to speculate that SR9009 has potential as a therapeutic agent for the treatment of PCOS.


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