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DOI: 10.1055/a-1073-2346
Dynamic Analysis of the Biochemical Changes in Rats with Polycystic Ovary Syndrome (PCOS) Using Urinary 1H NMR-Based Metabonomics
Funding Information: National Natural Science Foundation of China, Grant No. 81360555.Publikationsverlauf
received 23. September 2019
accepted 27. November 2019
Publikationsdatum:
16. Januar 2020 (online)
Abstract
Polycystic ovarian syndrome (PCOS) is the most common endocrine disease that causes reproductive abnormalities in fertile women. It is closely related to the persistent anovulatory, insulin resistance, and high androgen. However, the molecular mechanisms underlying the pathological development of PCOS are still unclear. In this study, we aimed to explore the distinctive metabolic patterns in insulin combined with human chorionic gonadotrophin induced PCOS. The dynamic changes of endogenous metabolites in the development of PCOS were studied using untargeted metabolomic approaches based on nuclear magnetic resonance. The results showed that the degree of PCOS disorder metabolites at different periods was not exactly the same. Twelve significantly differential endogenous metabolites from different time points were selected as potential biomarkers relate to pathological process of PCOS. Among them, six metabolites showed a good diagnostic accuracy with PCOS model. The arginine and proline metabolic pathway was considered as one of the most crucial pathways that affects occurrence and development of PCOS. In addition, IRS-1, Akt, PI3K, IκB, and NF-κB (p65) were significantly changed in the ovary tissue of PCOS rats, which revealed that the IRS-1-PI3K/Akt and NF-κB signal pathway may be involved in the development of PCOS. This study demonstrated that metabolomic analysis is a powerful tool for providing novel insight into understanding the pathogenesis of PCOS and provide a basic reference for the diagnosis of PCOS at the onset stage.
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References
- 1 Wei Z, Cao Y, Cong L. et al. Retraction notice to Effect of metformin pretreatment on pregnancy outcome of in vitro matured oocytes retrieved from women with polycystic ovary syndrome. Fertil Steril 2015; 104: 1048-1048
- 2 Azziz R, Woods KS, Reyna R. et al. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 2004; 89: 2745-2749
- 3 Himelein MJ, Thatcher SS. Polycystic ovary syndrome and mental health: A review. Obstetr Gynecol Surv 2006; 61: 723
- 4 Azziz R, Carmina E, Dewailly D. et al. Criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: An Androgen Excess Society guideline. J Clin Endocrinol Metab 2006; 91: 4237-4245
- 5 Zhang Y, Liu L, Yin TL. et al. Follicular metabolic changes and effects on oocyte quality in polycystic ovary syndrome patients. Oncotarget 2017; 8: 80472-80480
- 6 Steinberg HO, Brechtel G, Johnson A. et al. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest 1994; 94: 1172-1179
- 7 Artunc F, Schleicher E, Weigert C. et al. The impact of insulin resistance on the kidney and vasculature. Nat Rev Nephrol 2016; 12: 721-737
- 8 Liu M, Gao J, Zhang Y. et al. Serum levels of TSP-1, NF-κB and TGF-β1 in polycystic ovarian syndrome (PCOS) patients in northern China suggest PCOS is associated with chronic inflammation. Clin Endocrinol 2016; 83: 913-922
- 9 Coen M, Holmes E, Lindon JC. et al. NMR-based metabolic profiling and metabonomic approaches to problems in molecular toxicology. Chem Res Toxicol 2007; 21: 9
- 10 Tian JS, Peng GJ, Gao XX. et al. Dynamic analysis of the endogenous metabolites in depressed patients treated with TCM formula Xiaoyaosan using urinary (1)H NMR-based metabolomics. J Ethnopharmacol 2014; 158: 1-10
- 11 Jiang L, Huang J, Wang Y. et al. Eliminating the dication-induced intersample chemical-shift variations for NMR-based biofluid metabonomic analysis. Analyst 2012; 137: 4209-4219
- 12 Ghosh S, Sengupta A, Sharma S. et al. Metabolic fingerprints of serum, brain, and liver are distinct for mice with cerebral and noncerebral malaria: A 1H NMR spectroscopy-based metabonomic study. J Proteome Res 2012; 11: 4992
- 13 Zhou YZ, Yan ML, Gao L. et al. Metabonomics approach to assessing the metabolism variation and gender gap of Drosophila melanogaster in aging process. Exp Gerontol 2017; 98: 110-119
- 14 Fornes R, Ormazabal P, Rosas C. et al. Changes in the expression of insulin signaling pathway molecules in endometria from polycystic ovary syndrome women with or without hyperinsulinemia. Molecular Medicine 2010; 16: 129
- 15 Wang FF, Pan JX. Hyperandrogenism Involved in Pathogenesis of Polycystic Ovary Syndrome. J Int Reprod Health/Family Planning. 2013; http://jfprhc.bmj.com/
- 16 Moran L, Teede H. Metabolic features of the reproductive phenotypes of polycystic ovary syndrome. Hum Reprod Update 2009; 15: 477-488
- 17 Livingstone C, Collison M. Sex steroids and insulin resistance. Clinical Science 2002; 102: 151-166
- 18 Ridker PM, Hennekens CH, Roitmanjohnson B. et al. Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men. Lancet 1998; 351: 88-92
- 19 Yang Z, Zheng Q, Shi Y. Correlation of C-reactive protein with carotid intima-media wall thickness and flow nediated dilatation in women with polycystic ovary syndrome. J Pract Obstetr Gynecol. 2009; 25(08): 468-471
- 20 Tong BC, Barbul A. Cellular and physiological effects of arginine. Mini Rev Med Chem 2004; 4: 823-832
- 21 Zhao Y, Fu L, Li R. et al. Metabolic profiles characterizing different phenotypes of polycystic ovary syndrome: plasma metabolomics analysis. BMC Med 2012; 10: 153
- 22 Zhang ZS, Dong S, Gao YF. et al. Effect of inositol and D-chiro-inositol on alcoholic fatty liver rats. China Food Additiv. 2014; (09): 85-90
- 23 Ahn CW, Kwon DY, Jun DS. et al. Enhancement of cysteine catabolism into taurine impacts glutathione homeostasis in rats challenged with ethanol. Amino Acids 2015; 47: 1273-1277
- 24 Achreja A. Metabolic shifts toward glutamine regulate tumor growth and invasion in ovarian cancer. Fertil Steril 2014; 728-728
- 25 Møller N, Meek S, Bigelow M. et al. The kidney is an important site for in vivo phenylalanine-to-tyrosine conversion in adult humans: A metabolic role of the kidney. Proc Natl Acad Sci U S A 2000; 97: 1242
- 26 Diamanti-Kandarakis E, Alexandraki K, Piperi C. et al. Inflammatory and endothelial markers in women with polycystic ovary syndrome. Eur J Clin Invest 2006; 36: 691-697
- 27 Koppenol WH, Bounds PL, Dang CV. Otto Warburg’s contributions to current concepts of cancer metabolism. Nat Rev Cancer 2011; 11: 325-337
- 28 Lin XF, Ri-Ran WU, Jing DU. et al. Value of free androgen index for diagnosis of hyperandrogenism in polycystic ovary syndrome. J Sun Yat-Sen Univ (Medical Sciences) 2010; 31: 391-396
- 29 Anna Miczke JS, Danuta P-M, Lucyna O. et al. Effect of L-arginine supplementation on insulin resistance and serum adiponectin concentration in rats with fat diet. Int J Clin Exp Med 2015; 8: 10358
- 30 Proctor SD, Kelly SE, Russell JC. A novel complex of arginine–silicate improves micro- and macrovascular function and inhibits glomerular sclerosis in insulin-resistant JCR:LA-cp rats. Diabetologia 2005; 48: 1925-1932
- 31 Pappalardo MA, Vita R, Di Bari F. et al. Gly972Arg of IRS-1 and Lys121Gln of PC-1 polymorphisms act in opposite way in polycystic ovary syndrome. J Endocrinol Invest 2017; 40: 367-376
- 32 Giandalia A, Pappalardo MA, Russo GT. et al. Influence of peroxisome proliferator-activated receptor-gamma exon 2 and exon 6 and insulin receptor substrate (IRS)-1 Gly972Arg polymorphisms on insulin resistance and beta-cell function in southern mediterranean women with polycystic ovary syndrome. J Clin Transl Endocrinol 2018; 13: 1-8