Quercetin modulates granulosa cell mRNA androgen receptor gene expression in dehydroepiandrosterone-induced polycystic ovary in Wistar rats via metabolic and hormonal pathways
-
Olugbemi T. Olaniyan
, Okoli Bamidele
Abstract
Background
It is estimated that about 5–10% of women suffer from polycystic ovarian syndrome (PCOS) which is a major cause of female reproductive dysfunction. This study examined the role of quercetin on dehydroepiandrosterone (DHEA)-induced PCO in Wistar rats.
Methods
Twenty-eight pre-pubertal female Wistar rats that are 21 days old weighing 16–21 g were sorted into four groups (n = 7). Group I served as control and was given distilled water only, Group II were injected with 6 mg/100 g BW of DHEA in 0.2 mL of corn oil subcutaneously, Group III received 100 mg/kg BW of quercetin orally and Group IV received 6 mg/100 g BW of DHEA in 0.2 mL of corn oil subcutaneously and 100 mg/kg BW of quercetin orally. Rats were sacrificed after 15 days by cervical dislocation method. Blood samples and ovaries were collected for hormonal, biochemical, and histopathological analysis and expressions of mRNA androgen receptor gene were determined using RT–qPCR. All data were analysed using one-way ANOVA.
Results
A significant decrease (p < 0.05) in the antioxidant and metabolic enzyme activity in the DHEA treated group was observed when compared with control. DHEA co-administration with quercetin showed a significant decrease in malondialdehyde and cytokines when compared with DHEA treated group. Also a significant increase in progesterone, metabolic and antioxidant enzyme activity was observed. The histopathology demonstrates a reduction in cystic and atretic cells, improved expression of BCl2, E-Cadherin and a decrease in Bax.
Conclusions
Quercetin alleviated DHEA-induced PCO. These effects could be attributed to its antioxidant property.
Acknowledgments
We thank Mr. Olumide Afolabi and African Biosciences Ltd for providing laboratory facilities and technical support for the execution of the gene expression study of this research. Also, we appreciate Solis Biodyne Ltd Estonia for supporting us with the extraction Kitz.
Research funding: The research did not receive any external funding (None declared).
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Ethical approval: The ethical approval on the animal act right was obtained from the Institutional Animal Care Committee of the same Institution. The experimental procedures were carried out in accordance with Institutional Animal Ethics Committee (IAEC) guidelines.
References
[1] Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al. The androgen excess and PCOS society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 2009;91:456–88.10.1016/j.fertnstert.2008.06.035Search in Google Scholar
[2] Franks S, Stark J Hardy K. Follicle dynamics and anovulation in polycystic ovary syndrome. H Reprdn Updts 2008;14:367–78.10.1093/humupd/dmn015Search in Google Scholar
[3] Norman RJ, Dewailly D, Legro RS, Hickey TE. Polycystic ovary syndrome. Lancet 2007;370:685–97.10.1016/S0140-6736(07)61345-2Search in Google Scholar
[4] Teede H, Deeks A, Moran L. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med 2010;8:41.10.1186/1741-7015-8-41Search in Google Scholar
[5] Murri M, Luque-Ramírez M, Insenser M, Ojeda-Ojeda M, Escobar-Morreale HF. Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis. Hum Reprod Update 2013;19:268–88.10.1093/humupd/dms059Search in Google Scholar
[6] Nasiri N, Moini A, Eftekhari-Yazdi P. Abdominal obesity can induce both systemic and follicular fluid oxidative stress independent from polycystic ovary syndrome. Europ J Obst Gynec Reprod Biol 2015;184:112–6.10.1016/j.ejogrb.2014.11.008Search in Google Scholar
[7] Agarwal A. Nallella KP. Allamaneni SS, Said TM Role of antioxidants in treatment of male infertility: an overview of the literature. Reprod Biomed 2004;8:616–27.10.1016/S1472-6483(10)61641-0Search in Google Scholar
[8] Elks J. The dictionary of drugs: chemical data: chemical data, structures and bibliographies. Springer, 2014:641.Search in Google Scholar
[9] Mo Q, Lu SF, Simon NG. Dehydroepiandrosterone and its metabolites: differential effects on androgen receptor trafficking and transcriptional activity. J Ster Biochem Mol Biol 2006;99:50–58.10.1016/j.jsbmb.2005.11.011Search in Google Scholar PubMed
[10] Schulman RA, Dean C. DHEA (Dehydroepiandrosterone) is a common hormone produced in the adrenal glands, the gonads, and the brain. Solve It With Supplements. New York City: Rodale, Inc., 2007:100.Search in Google Scholar
[11] Scott T. Concise encyclopedia biology. Walter de Gruyter, 1996:49.Search in Google Scholar
[12] Jonard S, Dewailly D. The follicular excess in polycystic ovaries, due to intra-ovarian hyperandrogenism, may be the main culprit for the follicular arrest. Hum Reprod Update 2004;10:107–17.10.1093/humupd/dmh010Search in Google Scholar PubMed
[13] Bahorun T, Soobrattee MA, Luximon-Ramma V, Aruoma OI. Free radicals and antioxidants in cardiovascular health and disease. Int J Med Update 2006;1:25–41.10.4314/ijmu.v1i2.39839Search in Google Scholar
[14] De Groot H. Reactive oxygen species in tissue injury. Hepatogastroentrology 1994;41:328–32.Search in Google Scholar
[15] Calamia KT. Current and future use of antiTNF agents in the treatment of autoimmune, inflammatory disorders. Adv Exp Med Biol 2003;528:54.Search in Google Scholar
[16] Çelik LS, Yurdun K, Ebru DY, Abdullah T, Kenan D, Ufuk ÖM. Effects of vitamin D on ovary in DHEA-treated PCOS rat model: a light and electron microscopic study. Ultrastruct Pathol 2018;42:55–64.10.1080/01913123.2017.1385668Search in Google Scholar
[17] van Herck H, Baumans V, Stafeu FR, Beynen AC. A questionnaire-based inventory of the orbital puncture method in The Netherlands. Scand J Lab Ani Sci 1992;19:189–90.Search in Google Scholar
[18] Kartha R, Krishnamurthy S. Factors affecting in-vitro lipid peroxidation in rat brain homogenate. Ind J Physiol Pharmacol 1978;22:44–52.Search in Google Scholar
[19] Varshney R, Kale RK. Effects of calmodulin antagonist on radiation-induced lipid peroxidation in microsomes. Int J Radn Biol 1990;58:733–43.10.1080/09553009014552121Search in Google Scholar
[20] Beauchamp C, Fridovich I. Superoxide dismutase, improved assay and an assay applicable to acrylamide gel. Anal Biochem 1971;44:276–87.10.1016/0003-2697(71)90370-8Search in Google Scholar
[21] Misra HP, Fridovich L. The role of superoxide anion in the auto oxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972;247:3170–5.10.1016/S0021-9258(19)45228-9Search in Google Scholar
[22] Valerino DM, McCormack JJ. Xanthine oxidase-mediated oxidation of epinephrine. Biochem Pharmacol 1971;20:47–55.10.1016/0006-2952(71)90470-9Search in Google Scholar
[23] Sinha AK. Colorimetric assay of catalase. Anal Biochem 1972;47:389–94.10.1016/0003-2697(72)90132-7Search in Google Scholar
[24] Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 1974;249:7130–9.10.1016/S0021-9258(19)42083-8Search in Google Scholar
[25] Jollow DJ, Michell JR Zampaglionic N, Gillete JR. Bromoibenzene – induced liver necrosis: protective role of glutathione and evidence for 3, 4-bromobenzene oxide as hepatotoxic metabolite. Pharmacology 1974;11:151–69.10.1159/000136485Search in Google Scholar
[26] Lowry DH, Rosenbrough NJ, Far AL, Randal RJ. Protein measurement with folin phenol reagent. J Biol Chem 1951;193:265–75.10.1016/S0021-9258(19)52451-6Search in Google Scholar
[27] Evans WH. Membrane adenosine triphosphatase of E. coli activation by calcium ions and inhibition by monovalent cations. J Bacteriol 1969;100:914–22.10.1128/jb.100.2.914-922.1969Search in Google Scholar PubMed PubMed Central
[28] Bonting SC. In: Membranes and ion transport. Bittar EE, editor. London: Wiley Interscience, 1970:257–63.Search in Google Scholar
[29] Bonting SL. Presence of enzyme system in mammalian tissues. Membranes and ion transport. London: Wiley – Interscience, 1970:25–8.Search in Google Scholar
[30] Joham AE, Teede HJ, Ranasinha S, Zoungas S, Boyle J. Prevalence of infertility and use of fertility treatment in women with polycystic ovary syndrome: data from a large community-based cohort study. J Womens Health 2015;24:299–307.10.1089/jwh.2014.5000Search in Google Scholar
[31] Dumesic DA, Lobo RA. Cancer risk and PCOS. Steroids 2013;78:782–5.10.1016/j.steroids.2013.04.004Search in Google Scholar
[32] Halliwell B. Oxidative stress and cancer: have we moved forward? Biochem J 2007;401:1–11.10.1042/BJ20061131Search in Google Scholar
[33] Ziech D, Franco R, Pappa A, Panayiotidis MI. ROS induced genetic and epigenetic alterations in human carcinogenesis. Mutat Res 2011;711:167–73.10.1016/j.mrfmmm.2011.02.015Search in Google Scholar
[34] Donkena KV, Young CY, Tindall DJ. Oxidative stress and DNA methylation in prostate cancer. Obstet Gynecol Int 2010;2010:1-14.10.1155/2010/302051Search in Google Scholar
[35] Fariba K, Seyyed MB, Arash K, Mohammadali T, Elahe OS, Amir AK, et al. Investigating the role of hydroalcoholic extract of Apium graveolens and Cinnamon zeylanicum on metabolically change and ovarian oxidative injury in a rat model of polycystic ovary syndrome. Int J Women’s Health Reprod Sci 2019;7:192–8.Search in Google Scholar
[36] Pisoschi AM, Pop A. The role of antioxidants in the chemistry of oxidative stress: a review. Eur J Med Chem 2015;97:55–74.10.1016/j.ejmech.2015.04.040Search in Google Scholar
[37] De Bont R, van Larebeke N. Endogenous DNA damage in humans: a review of quantitative data. Mutagenesis 2004;19:169–85.10.1093/mutage/geh025Search in Google Scholar
[38] Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R. Protein carbonyl groups as biomarkers of oxidative stress. Clinica Chimica Acta 2003;329:23–38.10.1016/S0009-8981(03)00003-2Search in Google Scholar
[39] Tezil T, Basaga H. Modulation of cell death in age-related diseases. Curr Pharm Design 2014;20:3052–67.10.2174/13816128113196660702Search in Google Scholar PubMed
[40] Riley PA. Free radicals in biology: oxidative stress and the effects of ionizing radiation. Int J Radn Biol 2010;65:27–33.10.1080/09553009414550041Search in Google Scholar PubMed
[41] Sakanashi Y, Oyama K, Matsui H, Oyama TB, Oyama TM, Nishimura Y, et al. Possible use of quercetin, an antioxidant, for protection of cells suffering from overload of intracellular Ca2+: a model experiment. Life Sci 2008;83:164–9.10.1016/j.lfs.2008.05.009Search in Google Scholar PubMed
[42] Alanbay I, Ercan CM, Sakinci M, Coksuer H, Ozturk M, Tapan S. A macrophage activation marker chitotriosidase in women with PCOS: does low-grade chronic inflammation in PCOS relate to PCOS itself or obesity? Arch Gynecol Obstet 2012;286:1065–71.10.1007/s00404-012-2425-0Search in Google Scholar PubMed
[43] Siti HN, Kamisah Y, Kamsiah J. The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review). Vas Pharmacol 2015;71:40–56.10.1016/j.vph.2015.03.005Search in Google Scholar PubMed
[44] Touyz RM. Molecular and cellular mechanisms in vascular injury in hypertension: role of angiotensin II. Curr Opin Nephrol Hyperten 2005;14:125–31.10.1097/00041552-200503000-00007Search in Google Scholar PubMed
[45] Dalhia A, Griselda I, Diana B, Natalia IC, Fernanda P, Marta T. Angiopoietins/TIE2 system and VEGF are involved in ovarian function in a DHEA rat model of polycystic ovary syndrome. Endocrinology 2012;153:3446–56.10.1210/en.2012-1105Search in Google Scholar PubMed
[46] Castro MC, Massa ML, Arbeláez LG, Schinella G, Gagliardino JJ, Francini F. Fructose-induced inflammation, insulin resistance and oxidative stress: a liver pathological triad effectively disrupted by lipoic acid. Life Sci 2017;137:1–6.10.1016/j.lfs.2015.07.010Search in Google Scholar PubMed
[47] Yang Y, Qiao J, Li R, Li M-Z. Is interleukin-18 associated with polycystic ovary syndrome? Reprod Biol Endocrinol 2011;9:7.10.1186/1477-7827-9-7Search in Google Scholar PubMed PubMed Central
[48] Spaczynski RZ, Arici A, Duleba AJ. Tumor necrosis factor-α stimulates proliferation of rat ovarian theca- interstitial cells. Biol Reprod 1999;61:993–8.10.1095/biolreprod61.4.993Search in Google Scholar PubMed
[49] Taylor PC, Williams RO Feldmann M. Tumour necrosis factor alpha as a therapeutic target for immune-mediated inflammatory diseases. Curr Opin Biotechnol 2004;15:557–63.10.1016/j.copbio.2004.09.005Search in Google Scholar PubMed
[50] Dunaif A, Segal KR, Shelley DR, Green G, Dobrjansky A, Licholai T. Evidence for distinctive and intrinsic defects in insulin action in polycystic ovary syndrome. Diabetes 1996;41:1257–66.10.2337/diab.41.10.1257Search in Google Scholar PubMed
[51] Driggers PH, Segars JH. Estrogen action and cytoplasmic signaling pathways. Part II: The role of growth factors and phosphorylation in estrogen signaling. Trends Endocrinol Metab 2002;13:422–7.10.1016/S1043-2760(02)00634-3Search in Google Scholar
[52] Seyed HA, Maryam M, Malihe S, Hamed S, Reza A, Hossein H, et al. The effect of Galega officinalis on hormonal and metabolic profile in a rat model of polycystic ovary syndrome. Int J Womens Health Reprod Sci 2018;6:276–82.10.15296/ijwhr.2018.46Search in Google Scholar
[53] Buss WW, Kopp DE, Middleton E. Flavonoids modulation of human neutrophil function. Allergy Clin Immunol 1984;73:801–9.10.1016/0091-6749(84)90450-0Search in Google Scholar
[54] Olugbemi TO, Olufadekemi TK, Yinusa R. Protective effects of methanol extract of Plukenetia conophora seeds and 4H-Pyran-4-One 2,3-dihydro-3,5-dihydroxy-6-methyl on the reproductive function of male Wistar rats treated with cadmium chloride. Braz J Assist Reprod 2018;22:289–300.Search in Google Scholar
[55] Misra RR, Smith GT, Waalkes MP. Evaluation of the direct genotoxic potential of cadmium in four different rodent cell lines. Toxicology 1998;126:103–14.10.1016/S0300-483X(98)00003-1Search in Google Scholar
[56] Qayyum I, Zubrow AB, Ashraf QM, Kubin J, Delivoria-Papadopoulos M, Mishra OP. Nitration as a mechanism of Na+, K+-ATPase modification during hypoxia in the cerebral cortex of the guinea pig fetus. Neurochem Res 2001;26:1163–9.10.1023/A:1012331108641Search in Google Scholar
[57] D’Ambrosio SM, Gibson-D’Ambrosio RE, Brady T, Oberyszyn AS Robertson FM. Mechanisms of nitric oxide-induced cytotoxicity in normal human hepatocytes. Environ Mol Mutagen 2001;37:46–54.10.1002/1098-2280(2001)37:1<46::AID-EM1005>3.0.CO;2-6Search in Google Scholar
[58] Franks S, Mason H, White D Willis D. Etiology of anovulation in polycystic ovary syndrome. Steroids 1998;63:306–7.10.1016/S0039-128X(98)00035-XSearch in Google Scholar
© 2020 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Editorial
- Anti-microbial stewardship: is it old wine in a new bottle?
- Reviews
- Tangeretin: a mechanistic review of its pharmacological and therapeutic effects
- Silymarin: not just another antioxidant
- Original Articles
- Melatonin ameliorates some biochemical alterations following ketoconazole administration in rats
- Quercetin modulates granulosa cell mRNA androgen receptor gene expression in dehydroepiandrosterone-induced polycystic ovary in Wistar rats via metabolic and hormonal pathways
- Comparative expression analysis of phospholipid binding protein annexina1 in nephrogenesis and kidney cancer
- Anthonotha macrophylla P. Beauv (Caesalpiniaceae) aqueous extract exhibits antiestrogenic effects in vitro and in vivo
- Urate crystals trigger B-cell receptor signal transduction and induce B-cell proliferation
- Effects of gabapentinoids on responses of primary cultures from rat dorsal root ganglia to inflammatory or somatosensory stimuli
- Anti-inflammatory potential of chia seeds oil and mucilage against adjuvant-induced arthritis in obese and non-obese rats
- Antiproliferative effects of combinational therapy of Lycopodium clavatum and quercetin in colon cancer cells
- Attenuation of oxidative stress and neurotoxicity involved in the antidepressant-like effect of the MK-801(dizocilpine) in Bacillus Calmette-Guerin-induced depression in mice
- 3-(Para-fluorobenzoyl)-propionic acid; a metabolite of haloperidol, reversed oestradiol valerate-induced uterine hyperplasia via modulation of oestrogen receptor signalling pathways in female Wistar rats
- Pharmacological evidence of Vitex thyrsiflora, Entandrophragma cylindricum, and Anonidium mannii used for the management of inflammation in Cameroon
- Mitigation of aflatoxin B1- and sodium arsenite-induced cytotoxicities in HUC-PC urinary bladder cells by curcumin and Khaya senegalensis
- Saccharum officinarum juice alters reproductive functions in male Wistar rats
- The effects of Pb on sperm parameters and sperm DNA fragmentation of men investigated for infertility
Articles in the same Issue
- Editorial
- Anti-microbial stewardship: is it old wine in a new bottle?
- Reviews
- Tangeretin: a mechanistic review of its pharmacological and therapeutic effects
- Silymarin: not just another antioxidant
- Original Articles
- Melatonin ameliorates some biochemical alterations following ketoconazole administration in rats
- Quercetin modulates granulosa cell mRNA androgen receptor gene expression in dehydroepiandrosterone-induced polycystic ovary in Wistar rats via metabolic and hormonal pathways
- Comparative expression analysis of phospholipid binding protein annexina1 in nephrogenesis and kidney cancer
- Anthonotha macrophylla P. Beauv (Caesalpiniaceae) aqueous extract exhibits antiestrogenic effects in vitro and in vivo
- Urate crystals trigger B-cell receptor signal transduction and induce B-cell proliferation
- Effects of gabapentinoids on responses of primary cultures from rat dorsal root ganglia to inflammatory or somatosensory stimuli
- Anti-inflammatory potential of chia seeds oil and mucilage against adjuvant-induced arthritis in obese and non-obese rats
- Antiproliferative effects of combinational therapy of Lycopodium clavatum and quercetin in colon cancer cells
- Attenuation of oxidative stress and neurotoxicity involved in the antidepressant-like effect of the MK-801(dizocilpine) in Bacillus Calmette-Guerin-induced depression in mice
- 3-(Para-fluorobenzoyl)-propionic acid; a metabolite of haloperidol, reversed oestradiol valerate-induced uterine hyperplasia via modulation of oestrogen receptor signalling pathways in female Wistar rats
- Pharmacological evidence of Vitex thyrsiflora, Entandrophragma cylindricum, and Anonidium mannii used for the management of inflammation in Cameroon
- Mitigation of aflatoxin B1- and sodium arsenite-induced cytotoxicities in HUC-PC urinary bladder cells by curcumin and Khaya senegalensis
- Saccharum officinarum juice alters reproductive functions in male Wistar rats
- The effects of Pb on sperm parameters and sperm DNA fragmentation of men investigated for infertility