scholarly journals Rhamnocitrin Ameliorates Ovarian Fibrosis Via PPARγ/TGF-β1/Smad Pathway to Repair Ovarian Function in Polycystic Ovary Syndrome Rats Running Title：rhamnocitrin Ameliorates Ovarian Fibrosis in Polycystic Ovary Syndrome Rats

2021 ◽  
Author(s):  
Yanyuan Zhou ◽  
Chunhua He ◽  
Zhewen Dong ◽  
Huan Lan ◽  
Chaojie Chong ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
Vaginal Smear ◽  
Endocrine Disorders ◽  
Ovary Syndrome ◽  
Mechanistic Investigation ◽  
Serum Hormone ◽  
Underlying Mechanisms ◽  
Tgf Β1

Abstract Background: Polycystic ovary syndrome (PCOS) is one of the major endocrine disorders in women, characterized by androgen excess, chronic anovulation and ovarian fibrosis. Rhamnocitrin is an herbal bioactive flavonoid that has anti-inflammation and antioxidant effects. We intended to investigate the impacts of Rhamnocitrin on PCOS-induced ovarian fibrosis and its underlying mechanisms.Methods: Dehydroepiandrosterone (DHEA) induced-PCOS rats were treated with Rhamnocitrin. HE staining was performed to detect ovarian histological features. Ovarian fibrosis was evaluated by Sirius Red and Masson staining. Vaginal smear was examined to exhibit estrus cycle stage and vaginal cornification. The serum hormone levels of FSH, LH, E2 and T were measured with ELISA. The related mRNAs and proteins of fibrosis factors and PPARγ/TGF-β1/Smad2 signaling were detected by RT-qPCR and western blot. The weights of rat bodies and ovaries were recorded. PPARγ inhibitor T0070907 and its agonist GW1929 were employed for the mechanistic investigation.Results: The corpus luteum and follicles were increased and irregular estrous cycle was restored after Rhamnocitrin treatment in PCOS rats. Rhamnocitrin inhibited ovarian fibrosis and down-regulated the expressions of fibrotic factors. Rhamnocitrin reduced the increased levels of LH, E2, and T, and elevated the decreased FSH level in PCOS rats. Besides, Rhamnocitrin elevated the down-regulated PPARγ, and suppressed the up-regulated TGF-β1 and p-Smad2 expressions induced by PCOS. These effects of Rhamnocitrin on PCOS rats could be antagonized by T0070907, whereas GW1929 markedly mimics the functions of Rhamnocitrin. Conclusions: Rhamnocitrin ameliorates ovarian fibrosis in PCOS rats through regulation PPARγ/TGF-β1/Smad2pathway, suggesting it can be a potentially effective therapeutic candidate for PCOS treatment.

Rhamnocitrin ameliorates ovarian fibrosis via PPARγ/TGF-β1/Smad2/3 pathway to repair ovarian function in polycystic ovary syndrome rats

2021 ◽  
Author(s):  
Yanyuan Zhou ◽  
Huan Lan ◽  
Zhewen Dong ◽  
Yaqi Wu ◽  
Chaojie Chong ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
Vaginal Smear ◽  
Endocrine Disorders ◽  
Ovary Syndrome ◽  
Mechanistic Investigation ◽  
Serum Hormone ◽  
Underlying Mechanisms ◽  
Tgf Β1

Abstract Background: Polycystic ovary syndrome (PCOS) is one of the major endocrine disorders in women, characterized by androgen excess, chronic anovulation and ovarian fibrosis. Rhamnocitrin is an herbal bioactive flavonoid that has anti-inflammation and antioxidant effects. We intended to investigate the impacts of Rhamnocitrin on PCOS-induced ovarian fibrosis and its underlying mechanisms.Methods:Dehydroepiandrosterone (DHEA) induced-PCOS rats were treated with Rhamnocitrin. HE staining was performed to detect ovarian histological features. Ovarian fibrosis was evaluated by Sirius Red and Masson staining. Vaginal smear was examined to exhibit estrus cycle stage and vaginal cornification. The serum hormone levels of FSH, LH, E2 and T were measured with ELISA. The related mRNAs and proteins of fibrosis factors and PPARγ/TGF-β1/Smad2/3 signaling were detected by RT-qPCR and western blot. The weights of rat bodies and ovaries were recorded. PPARγ inhibitor T0070907 and its agonist GW1929 were employed for the mechanistic investigation.Results:The corpus luteum and follicles were increased and irregular estrous cycle was restored after Rhamnocitrin treatment in PCOS rats. Rhamnocitrin inhibited ovarian fibrosis and down-regulated the expressions of fibrotic factors. Rhamnocitrin reduced the increased levels of LH, E2, and T, and elevated the decreased FSH level in PCOS rats. Besides, Rhamnocitrin elevated the down-regulated PPARγ, and suppressed the up-regulated TGF-β1 and p-Smad2/3 expressions induced by PCOS. These effects of Rhamnocitrin on PCOS rats could be antagonized by T0070907, whereas GW1929 markedly mimics the functions of Rhamnocitrin.Conclusions:Rhamnocitrin ameliorates ovarian fibrosis in PCOS rats through regulation PPARγ/TGF-β1/Smad2/3 pathway, suggesting it can be a potentially effective therapeutic candidate for PCOS treatment.

scholarly journals Family-Based Quantitative Trait Meta-Analysis Implicates Rare Noncoding Variants in DENND1A in Polycystic Ovary Syndrome

2019 ◽  
Vol 104 (9) ◽  
pp. 3835-3850 ◽  
Author(s):  
Matthew Dapas ◽  
Ryan Sisk ◽  
Richard S Legro ◽  
Margrit Urbanek ◽  
Andrea Dunaif ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Quantitative Trait ◽  
Rare Variants ◽  
Polycystic Ovary ◽  
Association Studies ◽  
Meta Analysis ◽  
Premenopausal Women ◽  
Endocrine Disorders ◽  
Genome Wide Association Studies ◽  
Ovary Syndrome

AbstractContextPolycystic ovary syndrome (PCOS) is among the most common endocrine disorders of premenopausal women, affecting 5% to15% of this population depending on the diagnostic criteria applied. It is characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. PCOS is highly heritable, but only a small proportion of this heritability can be accounted for by the common genetic susceptibility variants identified to date.ObjectiveThe objective of this study was to test whether rare genetic variants contribute to PCOS pathogenesis.Design, Patients, and MethodsWe performed whole-genome sequencing on DNA from 261 individuals from 62 families with one or more daughters with PCOS. We tested for associations of rare variants with PCOS and its concomitant hormonal traits using a quantitative trait meta-analysis.ResultsWe found rare variants in DENND1A (P = 5.31 × 10−5, adjusted P = 0.039) that were significantly associated with reproductive and metabolic traits in PCOS families.ConclusionsCommon variants in DENND1A have previously been associated with PCOS diagnosis in genome-wide association studies. Subsequent studies indicated that DENND1A is an important regulator of human ovarian androgen biosynthesis. Our findings provide additional evidence that DENND1A plays a central role in PCOS and suggest that rare noncoding variants contribute to disease pathogenesis.

scholarly journals Use of Inositols in Polycystic Ovary Syndrome

2020 ◽  
Vol 16 (28) ◽  
pp. 24-34
Author(s):  
O.A. Pustotina ◽  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
The Body ◽  
Metabolic Parameters ◽  
Ovary Syndrome ◽  
Pathogenetic Role

The article presents key data on the physiology of inositols in the body, their pathogenetic role in the development of polycystic ovary syndrome, and the possibilities of myo-inositol and D-chiro-inositol in the restoration of ovarian function, metabolic parameters, and overcoming of infertility.

scholarly journals Family-based quantitative trait meta-analysis implicates rare noncoding variants in DENND1A in pathogenesis of polycystic ovary syndrome

2018 ◽  
Author(s):  
Matthew Dapas ◽  
Ryan Sisk ◽  
Richard S. Legro ◽  
Margrit Urbanek ◽  
Andrea Dunaif ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Quantitative Trait ◽  
Rare Variants ◽  
Polycystic Ovary ◽  
Association Studies ◽  
Meta Analysis ◽  
Premenopausal Women ◽  
Endocrine Disorders ◽  
Genome Wide Association Studies ◽  
Ovary Syndrome

ABSTRACTPolycystic ovary syndrome (PCOS) is among the most common endocrine disorders of premenopausal women, affecting 5-15% of this population depending on the diagnostic criteria applied. It is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. PCOS is a leading risk factor for type 2 diabetes in young women. PCOS is highly heritable, but only a small proportion of this heritability can be accounted for by the common genetic susceptibility variants identified to date. To test the hypothesis that rare genetic variants contribute to PCOS pathogenesis, we performed whole-genome sequencing on DNA from 62 families with one or more daughters with PCOS. We tested for associations of rare variants with PCOS and its concomitant hormonal traits using a quantitative trait meta-analysis. We found rare variants in DENND1A (P=5.31×10−5, Padj=0.019) that were significantly associated with reproductive and metabolic traits in PCOS families. Common variants in DENND1A have previously been associated with PCOS diagnosis in genome-wide association studies. Subsequent studies indicated that DENND1A is an important regulator of human ovarian androgen biosynthesis. Our findings provide additional evidence that DENND1A plays a central role in PCOS and suggest that rare noncoding variants contribute to disease pathogenesis.

scholarly journals Simultaneous alterations in ovaries and bone as a result of Polycystic Ovary Syndrome

2021 ◽  
Vol 3 (2) ◽  
pp. 2-14
Author(s):  
Ana Lúcia de Oliveira Bonfá ◽  
Eduardo Donato Alves ◽  
Víctor Fabrício ◽  
Keico Okino Nonaka ◽  
Janete Aparecida Anselmo-Franci ◽  
...  
Keyword(s):  
Cell Culture ◽  
Animal Model ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Estradiol Valerate ◽  
Endocrine Disorders ◽  
Ovary Syndrome ◽  
Bone Properties ◽  
In Vivo Animal Model

Polycystic ovary syndrome (PCOS) is one of the most widely recognized endocrine disorders affecting reproductive-age women. The etiopathogenesis and mechanisms of this syndrome remain unclear. Diagnosis requires two of the following: polycystic ovaries, oligo- or anovulation, and hyperandrogenism. Most women with PCOS display conditions such as metabolic abnormalities, diabetes, obesity, cardiovascular disease, and/or bone dysfunction. Considering the ethical limitations of human studies, animal and cell culture models that reflect some features of PCOS are important for investigation of this syndrome. The aim of the present work was to study some of the endocrine relationships between ovaries and bone tissue in a polycystic ovary syndrome animal model. The study was performed using an estradiol valerate PCOS-induced rat model (n = 30) and bone mesenchymal stem cell cultured from bone marrow of those animals. It was hypothesized that changes of the endocrine relationship between ovaries and bones could be observed in from in vivo animal model and in vitro cell culture assays. The ovarian morphological and endocrine changes seem to be correlated with endocrine, biophysical, and biomechanical changes in bone properties. Mesenchymal stem cells obtained from PCOS-induced rats, cultured for up to 21 days and differentiated into osteoblasts, presented lower viability and reduced mineralization of the extracellular matrix. Taken together, these results indicate important endocrine and structural effects of PCOS in ovaries and bones, contributing to part of the understanding of the pathophysiological mechanisms of PCOS.

Rosiglitazone in insulin-resistant women with polycystic ovary syndrome (PCOS): effects on ovarian function and metabolism

2002 ◽  
Vol 78 ◽  
pp. S36 ◽  
Author(s):  
Nicholas A Cataldo ◽  
Fahim Abbasi ◽  
Tracey L McLaughlin ◽  
Patricia Y Fechner ◽  
Gerald M Reaven ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Insulin Resistant

Polycystic ovary syndrome

2020 ◽  
pp. 528-535
Author(s):  
Zhongwei Huang ◽  
Eu Leong Yong
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Endometrial Hyperplasia ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Endocrine Disorders ◽  
Age Group ◽  
Ovary Syndrome ◽  
Reproductive Ageing ◽  
Reproductive Age Group

Polycystic ovary syndrome (PCOS) is an enigmatic condition and its pathophysiology remains to be determined but it is likely to involve the androgen, insulin, and anti-Mullerian hormone pathways. PCOS is diagnosed in women in the reproductive age group based on the Rotterdam criteria. The spectrum of disease involves various phenotypes based on the current diagnostic criteria and this may have reproductive, metabolic, and endocrine consequences. Reproductive issues include that of irregular menstrual cycles and anovulation. Metabolic disorders such as insulin resistance, obesity, dyslipidaemia, and hypertension must be screened for in all women who are diagnosed with PCOS. Long-term risks of metabolic and endocrine disorders in women with PCOS still need further confirmation with more robust data. Reproductive ageing appears to be increased in women with PCOS and they seem to menopause at a later age. Thus far, PCOS appears to be associated with endometrial hyperplasia and cancer.

scholarly journals Metabolomic Insight into Polycystic Ovary Syndrome—An Overview

2020 ◽  
Vol 21 (14) ◽  
pp. 4853 ◽  
Author(s):  
Anna Rajska ◽  
Magdalena Buszewska-Forajta ◽  
Dominik Rachoń ◽  
Michał Jan Markuszewski
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Metabolic Pathways ◽  
Polycystic Ovary ◽  
Review Article ◽  
Endocrine Disorders ◽  
Crucial Aspect ◽  
Ovary Syndrome ◽  
Metabolic Markers ◽  
Insight Into ◽  
Potential Biomarkers

Searching for the mechanisms of the polycystic ovary syndrome (PCOS) pathophysiology has become a crucial aspect of research performed in the last decades. However, the pathogenesis of this complex and heterogeneous endocrinopathy remains unknown. Thus, there is a need to investigate the metabolic pathways, which could be involved in the pathophysiology of PCOS and to find the metabolic markers of this disorder. The application of metabolomics gives a promising insight into the research on PCOS. It is a valuable and rapidly expanding tool, enabling the discovery of novel metabolites, which may be the potential biomarkers of several metabolic and endocrine disorders. The utilization of this approach could also improve the process of diagnosis and therefore, make treatment more effective. This review article aims to summarize actual and meaningful metabolomic studies in PCOS and point to the potential biomarkers detected in serum, urine, and follicular fluid of the affected women.

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