Effect of quercetin on steroidogenesis and folliculogenesis in ovary of mice with experimentally-induced polycystic ovarian syndrome

Introduction Polycystic Ovary syndrome (PCOS) affects the health of many women around theworld. Apart from fundamental metabolic problems connected to PCOS, focus of our study is on the role of quercetin on genes relevant to steroidogenesis and folliculogenesis. Methods Eighteen mature parkes strain mice (4-5 weeks old) weighing18–21 g were randomly divided into three groups of six each as follows: Group I serves as the control and was given water and a regular chow diet ad lib for 66 days; group II was given oral gavage administration of letrozole (LETZ) (6 mg/kgbw) for 21 days to induce PCOS and was left untreated for 45 days; For three weeks, Group III received oral gavage dose of LETZ (6 mg/kg), after which it received Quercetin (QUER) (125 mg/kg bw orally daily) for 45 days. Results In our study we observed that mice with PCOS had irregular estrous cycle with increased LH/FSH ratio, decreased estrogen level and decline in expression of Kitl, Bmp1, Cyp11a1, Cyp19a1, Ar, lhr, Fshr and Esr1 in ovary. Moreover, we observed increase in the expression of CYP17a1, as well as increase in cholesterol, triglycerides, testosterone, vascular endothelial growth factor VEGF and insulin levels. All these changes were reversed after the administration of quercetin in PCOS mice. Discussion Quercetin treatment reversed the molecular, functional and morphological abnormalities brought on due to letrozole in pathological and physiological setting, particularly the issues of reproduction connected to PCOS. Quercetin doesn’t act locally only but it acts systematically as it works on Pituitary (LH/FSH)- Ovary (gonad hormones) axis. the Side effects of Quercetin have to be targeted in future researches. Quercetin may act as a promising candidate for medical management of human PCOS.

[1]  V. Shrivastava,et al.  The hypoglycemic and anti-hyperlipidemic activity of vitamin C in di(2-ethylhexyl) phthalate-induced toxicity in female mice, Mus musculus , 2023, Comparative Clinical Pathology.

[2]  V. Shrivastava,et al.  Ameliorative effects of quercetin on endocrine and metabolic abnormalities associated with experimentally induced polycystic ovary syndrome in mice , 2023, Comparative Clinical Pathology.

[3]  S. Muzamil,et al.  Gallic acid reverses ovarian disturbances in mice with letrozole-induced PCOS via modulating Adipo R1 expression , 2022, Toxicology reports.

[4]  S. Tiwari,et al.  Advances on nanoformulation approaches for delivering plant-derived antioxidants: A case of quercetin. , 2022, International journal of pharmaceutics.

[5]  Chaoying Wang,et al.  Potential Role of Quercetin in Polycystic Ovary Syndrome and Its Complications: A Review , 2022, Molecules.

[6]  V. Shrivastava,et al.  Metformin treatment ameliorates endocrine-metabolic disturbances in letrozole-induced PCOS mice model by modulating adiponectin status , 2022, Obesity Medicine.

[7]  J. Cohen‐Tannoudji,et al.  Estradiol Signaling at the Heart of Folliculogenesis: Its Potential Deregulation in Human Ovarian Pathologies , 2022, International journal of molecular sciences.

[8]  P. Gasque,et al.  Focus on the high therapeutic potentials of quercetin and its derivatives , 2022, Phytomedicine Plus.

[9]  V. Shrivastava,et al.  Turmeric extract alleviates endocrine-metabolic disturbances in letrozole-induced PCOS by increasing adiponectin circulation: A comparison with Metformin , 2021, Metabolism Open.

[10]  Asmaa M Elfiky,et al.  The anti-androgenic effect of quercetin on hyperandrogenism and ovarian dysfunction induced in a dehydroepiandrosterone rat model of polycystic ovary syndrome , 2021, Steroids.

[11]  Yanxia Chen,et al.  Mechanism of quercetin on the improvement of ovulation disorder and regulation of ovarian CNP/NPR2 in PCOS model rats. , 2021, Journal of the Formosan Medical Association = Taiwan yi zhi.

[12]  Z. Saadia Follicle Stimulating Hormone (LH: FSH) Ratio in Polycystic Ovary Syndrome (PCOS) - Obese vs. Non- Obese Women , 2020, Medical archives.

[13]  Ming-Xing Wang,et al.  A Rat Model of Polycystic Ovary Syndrome with Insulin Resistance Induced by Letrozole Combined with High Fat Diet , 2020, Medical science monitor : international medical journal of experimental and clinical research.

[14]  M. Alizadeh,et al.  Quercetin and polycystic ovary syndrome, current evidence and future directions: a systematic review , 2020, Journal of Ovarian Research.

[15]  U. Zafar,et al.  Prevalence of PCOS with Associated Symptoms and Complications at Tertiary Care Hospital of Karachi , 2019, Journal of Advances in Medicine and Medical Research.

[16]  F. Zal,et al.  Amelioration by quercetin of insulin resistance and uterine GLUT4 and ERα gene expression in rats with polycystic ovary syndrome (PCOS). , 2019, Reproduction, fertility, and development.

[17]  Alshaymaa Amin Zaki El-Bahya A Closer Insight into The Role of Vitamin D in Polycystic Ovary Syndrome (Pcos) , 2018, Global Journal of Pharmacy & Pharmaceutical Sciences.

[18]  H. Lee,et al.  Licorice ethanol extract improves symptoms of polycytic ovary syndrome in Letrozole-induced female rats , 2018, Integrative medicine research.

[19]  F. Otsuka,et al.  A regulatory role of androgen in ovarian steroidogenesis by rat granulosa cells , 2017, The Journal of Steroid Biochemistry and Molecular Biology.

[20]  W. Almawi,et al.  Analysis of VEGFA Variants and Changes in VEGF Levels Underscores the Contribution of VEGF to Polycystic Ovary Syndrome , 2016, PloS one.

[21]  M. Nourbakhsh,et al.  Effects of Quercetin on Adiponectin-Mediated Insulin Sensitivity in Polycystic Ovary Syndrome: A Randomized Placebo-Controlled Double-Blind Clinical Trial , 2016, Hormone and Metabolic Research.

[22]  D. Dewailly,et al.  Interactions between androgens, FSH, anti-Müllerian hormone and estradiol during folliculogenesis in the human normal and polycystic ovary. , 2016, Human reproduction update.

[23]  Snehal S. Patel,et al.  Phosphatidylinositide 3-kinase inhibition: A new potential target for the treatment of polycystic ovarian syndrome , 2016, Pharmaceutical biology.

[24]  L. Lenghel,et al.  Letrozole vs estradiol valerate induced PCOS in rats: glycemic, oxidative and inflammatory status assessment. , 2016, Reproduction.

[25]  Y. I. Muzib,et al.  A novel method of extraction of bamboo seed oil (Bambusa bambos Druce) and its promising effect on metabolic symptoms of experimentally induced polycystic ovarian disease , 2016, Indian journal of pharmacology.

[26]  S. Zoungas,et al.  Prevalence of infertility and use of fertility treatment in women with polycystic ovary syndrome: data from a large community-based cohort study. , 2015, Journal of women's health.

[27]  Jie Chen,et al.  The correlation of aromatase activity and obesity in women with or without polycystic ovary syndrome , 2015, Journal of Ovarian Research.

[28]  Ho-Joon Lee,et al.  Androgens regulate ovarian follicular development by increasing follicle stimulating hormone receptor and microRNA-125b expression , 2014, Proceedings of the National Academy of Sciences.

[29]  Yin Shi,et al.  Effects of Electro-Acupuncture on Ovarian P450arom, P450c17α and mRNA Expression Induced by Letrozole in PCOS Rats , 2013, PloS one.

[30]  G. Fraizer,et al.  Androgen up-regulates vascular endothelial growth factor expression in prostate cancer cells via an Sp1 binding site , 2013, Molecular Cancer.

[31]  S. Saito,et al.  Kami‐shoyo‐san, Kampo (Japanese traditional medicine), is effective for climacteric syndrome, especially in hormone‐replacement‐therapy‐resistant patients who strongly complain of psychological symptoms , 2013, The journal of obstetrics and gynaecology research.

[32]  A. Bremer Polycystic ovary syndrome in the pediatric population. , 2010, Metabolic syndrome and related disorders.

[33]  Martin M Matzuk,et al.  The mammalian ovary from genesis to revelation. , 2009, Endocrine reviews.

[34]  Wei Zhang,et al.  Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. , 2009, The Journal of clinical investigation.

[35]  V. Cela,et al.  Vascular endothelial growth factor and its soluble receptor in patients with polycystic ovary syndrome undergoing IVF , 2009, Human fertility.

[36]  J. Shaw,et al.  Cardiometabolic risk in polycystic ovary syndrome: a comparison of different approaches to defining the metabolic syndrome. , 2008, Human reproduction.

[37]  A. Papavassiliou,et al.  Pathophysiology and types of dyslipidemia in PCOS , 2007, Trends in Endocrinology & Metabolism.

[38]  R. Azziz,et al.  Diagnosis of Polycystic Ovary Syndrome , 2007, Clinical obstetrics and gynecology.

[39]  H. Ortega,et al.  Microscopic characterization of follicular structures in letrozole-induced polycystic ovarian syndrome in the rat. , 2006, Archives of medical research.

[40]  D. Abbott,et al.  Androgen excess fetal programming of female reproduction: a developmental aetiology for polycystic ovary syndrome? , 2005, Human reproduction update.

[41]  H. Kafalı,et al.  Letrozole-induced polycystic ovaries in the rat: a new model for cystic ovarian disease. , 2004, Archives of medical research.

[42]  S. Franks,et al.  Developmental origin of polycystic ovary syndrome - a hypothesis. , 2002, The Journal of endocrinology.

[43]  J. George,et al.  Current Concepts of Follicle-Stimulating Hormone Receptor Gene Regulation1 , 2011, Biology of reproduction.

[44]  open access to scientific and medical research Open Access Full Text Article Review Treatment options for polycystic ovary syndrome , 2022 .