Endocrine, Metabolic and Ovarian Features of Human PCO Repeat in Sprague Dawley Rats- An Experimental Study


Affiliations

  • St. Thomas College, Research Department of Zoology, Kozhencherry, Kerala, 689642, India
  • Pushpagiri Research Centre, Pushpagiri Institute of Medical Sciences, Molecular Biology and Phytoceuticals Research Laboratory, Thiruvalla, Kerala, 689101, India

Abstract

Polycystic Ovary Syndrome (PCOS) affects 9-18 % of women in the reproductive age group, and is manifested as hyperandrogenism and infertility. However, the etiology of PCOS is still not clear, so knowledge from experimental animal models may perhaps enhance the knowledge regarding the mechanisms of establishment and advancement of PCOS. The present study was undertaken to validate the role of high fructose intake and the consequent alterations in the hormone levels as the causative factors of polycystic ovaries in females. Healthy, young colony-bred female albino rats, Sprague Dawley breed, weighing 80-85 g, were divided into three groups. Rats in group I served as placebo control. Group II rats received fructose, 10 g/10 mL/kg body weight (bw) per day through oral gavage. Group III rats received ip injection of insulin at 0.5 IU/kg bw/day. The treatment lasted 90 days. A significant (p<0.05) increase was detected in FSH, LH, insulin, testosterone and estradiol levels in fructose- and insulin-treated animals compared to the control. The levels of blood glucose, protein, cholesterol and triglyceride were significantly (p<0.05) increased in the treated groups. Cytoplasmic vacuolation, altered hepatic sinusoids, hepatic necrosis, etc., were observed in liver sections of treated rats. The histoarchitecture of ovary of treated animals presented fluid-filled cysts without granulosa cells and follicles. In the treated animals, histolpathological examination of fallopian tubal segments revealed infiltration of inflammatory cells with harshly crowded epithelial cells. Thus, fructose and insulin treatments reiterate certain endocrine, metabolic and ovarian characteristics of human polycystic ovary in therat.

Keywords

Estradiol, Histoarchitecture, Polycystic Ovarian Syndrome, Testosterone

Full Text:

References

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; 89:2745-49. https://doi.org/10.1210/jc.2003-032046 PMid:15181052

DeUgarte CM, Bartolucci AA, Azziz R. Prevalence of insulin resistance in the polycystic ovary syndrome using the homeostasis model assessment. Fertil Steril. 2005; 83:1454-60. https://doi.org/10.1016/j.fertnstert.2004.11.070 PMid: 15866584

Ehrmann DA, Barnes RB, Rosenfield RL, et al. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care. 1999; 22:141-46. https://doi.org/10.2337/diacare.22.1.141 PMid:10333916

Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol. 2011; 7:219-31. https://doi.org/10.1038/nrendo.2010.217 PMid:21263450

Larsson I, Hulthén L, Landén M, et al. Dietary intake, resting energy expenditure, and eating behavior in women with and without polycystic ovary syndrome. Clin Nutr. 2016; 35:213-18. https://doi.org/10.1016/j.clnu.2015.02.006 PMid:25743212

Pasquali R, Gambineri A. Role of changes in dietary habits in polycystic ovary syndrome. Reprod Biomed Online. 2004; 8:431-39. https://doi.org/10.1016/S1472-6483(10)60927-3

Gambineri A, Pelusi C, Genghini S, et al. Effect of flutamide and metformin administered alone or in combination in dieting obese women with polycystic ovary syndrome. Clin Endocrinol (Oxf). 2004; 60:241-49. https://doi.org/10.1111/j.1365- 2265.2004.01973.x PMid:14725687

Malik VS, Popkin BM, Bray GA, et al. Sugar-sweetened beverages and risk of metabolic syndrome and type 2 diabetes: a metaanalysis. Diabetes Care. 2010; 33:2477-83. https://doi.org/10.2337/dc10-1079 PMid:20693348 PMCid:PMC2963518

World Health Organization. 2016. Global database on body mass index. World Health Organisation: Global strategy on diet, physical activity and health.

Stanhope KL, Medici V, Bremer AA, et al. A dose-response study of consuming high-fructose corn syrup-sweetened beverages on lipid/lipoprotein risk factors for cardiovascular disease in young adults. Am J Clin Nutr. 2015; 101:1144-54. https://doi. org/10.3945/ajcn.114.100461 PMid:25904601 PMCid:PMC4441807

Voznesenskaya A, Tordoff MG. Low-calcium diet prevents fructose-induced hyperinsulinemia and ameliorates the response to glucose load in rats. Nutr Metab (Lond). 2015; 12:38. https://doi.org/10.1186/s12986-015-0035-0 PMid:26516336 PMCid:PMC4625447

Maiolini R, Masseyeff R. Maiolini R, et al. A sandwich method of enzyme immunoassay. I. Application to rat and human alphafetoprotein. J. Immunol. Methods.1975; 8(3):223-34. https://doi.org/10.1016/0022-1759(75)90115-5

Krall LP, Beaser RS. Joslin Diabetes Manual. Philadelphia: Lea and Febiger. 1989; 138.

Zlatkis A, Zak B, Boyle AJ. A new method for the direct determination of serum cholesterol. J Lab Clin Med. 1953; 41(3):486-92.

Lowry OH, Rosebrough NJ, Farr Al, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193:265- 75. https://doi.org/10.1016/S0021-9258(19)52451-6

Jacobs NJ, VanDenmark PJ. The purification and properties of the alpha-glycerophosphate-oxidizing enzyme of Streptococcus faecalis 10C1. Arch Biochem Biophys. 1960; 88:250-55. https://doi.org/10.1016/0003-9861(60)90230-7

Di Nicolantonio JJ, O’Keefe JH, Lucan SC. Added fructose: a principal driver of type 2 diabetes mellitus and its consequences. Mayo Clin Proc. 2015; 90:372-81. https://doi.org/10.1016/j.mayocp.2014.12.019 PMid:25639270

Malik VS, Hu FB. Fructose and Cardiometabolic Health: What the Evidence From Sugar-Sweetened Beverages Tells Us. J Am Coll Cardiol. 2015; 66:1615-24. https://doi.org/10.1016/j.jacc.2015.08.025 PMid:26429086 PMCid: PMC4592517

Bray GA. How bad is fructose? Am J Clin Nutr. 2007; 86:895-96. https://doi.org/10.1093/ajcn/86.4.895 PMid:17921361

American Diabetes Association, Bantle JP, Wylie-Rosett J, Albright AL, et al. Nutrition recommendations and interventions for diabetes: A position statement of the American Diabetes Association. Diabetes Care. 2008; 1:S61-78. https://doi.org/10.2337/ dc08-S061 PMid:18165339

De Leo V, la Marca A, Petraglia F. Insulin-lowering agents in the management of polycystic ovary syndrome. Endocr Rev. 2003; 24:633-67. https://doi.org/10.1210/er.2002-0015 PMid:14570747

Qiao J, Feng HL. Extra- and intra-ovarian factors in polycystic ovary syndrome: Impact on oocyte maturation and embryo developmental competence. Hum Reprod Update. 2011; 17:17-33. https://doi.org/10.1093/humupd/dmq032 PMid:20639519 PMCid:PMC3001338

Arikawe AP, Daramola AO, Morakinyo, AO, Obika LFO, Effects of diabetes and insulin resistance on estrous cycle, corpus luteum function and pregnancy in female rats. Pak J Pathol. 2008; 19:38-43.

Arikawe AP, Iranloye BO, Ogunsola AO, Daramola AO. Chronic fructose consumption as a model of polycystic ovary syndrome in pregnant female Sprague-Dawley Rats. Afr J Biomed Res. 2012; 15:7-13.

Torres PJ, Skarra DV, Ho BS, et al. Letrozole treatment of adult female mice results in a similar reproductive phenotype but distinct changes in metabolism and the gut microbiome compared to pubertal mice. BMC Microbiol. 2019; 19:57. https://doi.org/10.1186/ s12866-019-1425-7 PMid:30871463 PMCid:PMC6419356

Patel R, Shah G. High-fat diet exposure from pre-pubertal age induces Polycystic Ovary Syndrome (PCOS) in rats. Reproduction. 2018; 155:141-51. https://doi.org/10.1530/REP-17-0584PMid:29196492

Nestler JE, Jakubowicz DJ, de Vargas AF, et al. Insulin stimulates testosterone biosynthesis by human thecal cells from women with polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system. J Clin Endocrinol Metab. 1998; 83:2001-5 https://doi.org/10.1210/jcem.83.6.4886

Diamanti-Kandarakis E, Papavassiliou AG. Molecular mechanisms of insulin resistance in polycystic ovary syndrome. Trends Mol Med. 2006; 12:324-32. https://doi.org/10.1016/j.molmed.2006.05.006 PMid:16769248

Nelson VL, Qin KN, Rosenfield RL, Wood JR, Penning TM, Legro RS, Strauss JF 3rd, McAllister JM. The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome. J Clin Endocrinol Metab. 2001; 86:5925-33. https://doi.org/10.1210/jcem.86.12.8088 PMid:11739466

Stanhope KL, Schwarz JM, Keim NL, et al. Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J Clin Invest. 2009; 119:1322-34. https://doi. org/10.1172/JCI37385 PMid:19381015 PMCid:PMC2673878

Aeberli I, Hochuli M, Gerber PA, et al. Moderate amounts of fructose consumption impair insulin sensitivity in healthy young men: A randomized controlled trial. Diabetes Care 2013; 36:150-56. https://doi.org/10.2337/dc12-0540 PMid:22933433 PMCid:PMC3526231

Schwarz JM, Noworolski SM, Wen MJ, et al. Effect of a high-fructose weight-maintaining diet on lipogenesis and liver fat. J Clin Endocrinol Metab. 2015; 100:2434-42. https://doi.org/10.1210/jc.2014-3678 PMid:25825943 PMCid:PMC4454806

Jürgens H, Haass W, Castañeda TR, et al. Consuming fructose-sweetened beverages increases body adiposity in mice. Obes Res. 2005; 13:1146-56. https://doi.org/10.1038/oby.2005.136 PMid:16076983

Basciano H, Federico L, Adeli K. Fructose, insulin resistance, and metabolic dyslipidemia. Nutr Metab. 2005; 2:5. https://doi. org/10.1186/1743-7075-2-5 PMid:15723702 PMCid:PMC552336

Lanaspa MA, Ishimoto T, Li N, et al. Endogenous fructose production and metabolism in the liver contributes to the development of metabolic syndrome. Nat Commun. 2013; 4:2434. https://doi.org/10.1038/ncomms3434 PMid:24022321

Johnson RJ, Nakagawa T, Sanchez-Lozada LG, et al. Sugar, uric acid, and the etiology of diabetes and obesity. Diabetes. 2013; 62:3307-15. https://doi.org/10.2337/db12-1814 PMid:24065788 PMCid:PMC3781481

Nakagawa T, Hu H, Zharikov S, et al. Causal role for uric acid in fructose-induced metabolic syndrome. Am J Physiol Renal Physiol. 2006; 290:F625-F631. https://doi.org/10.1152/ajprenal.00140.2005 PMid:16234313

Sautin YY, Johnson RJ. Uric acid: The oxidant-antioxidant paradox. Nucleosides Nucleotides Nucleic Acids. 2008; 27:608-01. https://doi.org/10.1080/15257770802138558 PMid:18600514 PMCid:PMC2895915

Taiwo IA, Adebesin OA, Shittu AF, et al. Glycaemic Activity of Ficus exasperate in Fructose- induced Glucose Intolerance in Rats. Researcher. 2010; 2:80-3.

Shahraki MR, Harati M, Shahraki AR. Prevention of high fructose-induced metabolic syndrome in male Wistar rats by aqueous extract of Tamarindus indica seed. Acta Med Iran. 2011; 49:277-83.

Babacanoglu C, Yildirim N, Sadi G, et al. Resveratrol prevents high-fructose corn syrup-induced vascular insulin resistance and dysfunction in rats. Food Chem Toxicol. 2013; 60:160-7. https://doi.org/10.1016/j.fct.2013.07.026 PMid:23872130

Alzamendi A, Giovambattista A, Raschia A, et al. Fructose-rich diet-induced abdominal adipose tissue endocrine dysfunction in normal male rats. Endocrine. 2009; 35:227-32. https://doi.org/10.1007/s12020-008-9143-1 PMid:19165636

Catena C, Giacchetti G, Novello M, et al. Cellular mechanisms of insulin resistance in rats with fructose-induced hypertension. Am J Hypertens. 2003; 16:973-78. https://doi.org/10.1016/S0895-7061(03)01002-1

Ueno M, Bezerra RM, Silva MS, et al. A high-fructose diet induces changes in phosphorylation in muscle and liver of rats. Braz J Med Biol Res. 2000; 33:1421-27. https://doi.org/10.1590/S0100-879X2000001200004 PMid:11105093

Dornas WC, de Lima WG, Pedrosa ML, Silva ME. Health implications of high-fructose intake and current research. Adv Nutr. 2015; 6:729-37. https://doi.org/10.3945/an.114.008144 PMid:26567197 PMCid:PMC4642413

Stanhope KL. Role of fructose-containing sugars in the epidemics of obesity and metabolic syndrome. Annu Rev Med. 2012; 63:329-43. https://doi.org/10.1146/annurev-med-042010-113026 PMid:22034869

Teff KL, Elliott SS, Tschöp M, et al. Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. J Clin Endocrinol Metab. 2004; 89:2963-72 https://doi.org/10.1210/jc.2003-031855 PMid:15181085

Prieto PG, Cancelas J, Villanueva-Peñacarrillo ML, et al. Plasma D-glucose, D-fructose and insulin responses after oral administration of D-glucose, D-fructose and sucrose to normal rats. J Am CollNutr. 2004: 23:414-9. https://doi.org/10.1080/07 315724.2004.10719386 PMid:15466948

Hayashi AA, Webb J, Choi J, et al. Intestinal SR-BI is upregulated in insulin-resistant states and is associated with overproduction of intestinal apoB48-containing lipoproteins. Am J Physiol Gastrointest Liver Physiol. 2011; 301:G326-37. https://doi.org/10.1152/ ajpgi.00425.2010 PMid:21546579

Ko EA, Kim HR, Kim YB, et al. Effect of High Fructose Corn Syrup (HFCS) intake on the female reproductive organs and lipid accumulation in adult rats. Dev Reprod. 2017: 21:151-56. https://doi.org/10.12717/DR.2017.21.2.151 PMid:28785736 PMCid:PMC5532307

Tappy L, Le KA. Metabolic effects of fructose and the worldwide increase in obesity. Physiol Rev. 2010; 90:23-46. https://doi. org/10.1152/physrev.00019.2009 PMid:20086073

Akintayo CO, Anjola JD. Letrozole and/or fructose induced-polycystic ovarian syndrome in animal model. FASEB J. 2017; 31:1.

Vani DH, Gopalan S, Manikandan, Vijayakumar V. Letrozole and fructose-induced polycystic ovaries in the rat: a novel model exhibiting both ovarian and metabolic characteristics for polycystic ovary syndrome in rat. Int J Pharm Sci Res. 2018; 11:2238-43

Wilson RD, Islam MS. Fructose-fed streptozotocin-injected rat: An alternative model for type 2 diabetes. Pharmacol Rep. 2012; 64:129-39. https://doi.org/10.1016/S1734-1140(12)70739-9


Refbacks

  • There are currently no refbacks.