Login Register Cart 0
Generic placeholder image

Current Drug Therapy

Editor-in-Chief

ISSN (Print): 1574-8855
ISSN (Online): 2212-3903

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

A Comprehensive Review of Preclinical Models for Polycystic Ovary Syndrome

Author(s): G. Santhana Kumar*, Kritika Garg, Arun Soni and Mittal Dalal

Volume 19, Issue 4, 2024

Published on: 05 October, 2023

Page: [426 - 437] Pages: 12

DOI: 10.2174/0115748855248659230922111800

Price: $65

Abstract

Background: Polycystic ovary syndrome (PCOS) is a reproductive, metabolic, and endocrine disorder with unclear aetiology. PCOS, the most common cause of female reproductive and metabolic disorders, is known to affect more than one in ten women globally. PCOS and associated clinical manifestations are probably underdiagnosed despite their high occurrence.

Objectives: Alternative animal models have been employed to investigate the causes of PCOS or assess potential treatments. In light of this piece of information, it is challenging to create an animal model that accurately captures all components of this condition; nonetheless, the resemblance of an animal model's biology and/or biochemical characteristics to the phenotypes of PCOS in humans may boost its applicability.

Results: The key characteristics of these models are closer to human situations when compared to women with PCOS, as shown by this comparison. The creation and testing of drugs for the treatment of PCOS are necessary.

Conclusion: The overview of PCOS, current preclinical models, and appropriate models chosen in different studies to mimic various phenotypes in PCOS studies are all covered in this review paper. Additionally, we have outlined the benefits and drawbacks of PCOS animal models.

« Previous Next »
Graphical Abstract

[1]
Bulsara J, Patel P, Soni A, Acharya S. A review: Brief insight into polycystic ovarian syndrome. Endocrine and Metabolic Science 2021; 3: 100085.
[http://dx.doi.org/10.1016/j.endmts.2021.100085]
[2]
Escobar-Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol 2018; 14(5): 270-84.
[http://dx.doi.org/10.1038/nrendo.2018.24] [PMID: 29569621]
[3]
Baldani DP, Skrgatic L, Ougouag R. Polycystic ovary syndrome: Important underrecognised cardiometabolic risk factor in reproductive-age women. Int J Endocrinol 2015; 2015: 1-17.
[http://dx.doi.org/10.1155/2015/786362] [PMID: 26124830]
[4]
Escobar-Morreale HF, Álvarez-Blasco F, Botella-Carretero JI, Luque-Ramírez M. The striking similarities in the metabolic associations of female androgen excess and male androgen deficiency. Hum Reprod 2014; 29(10): 2083-91.
[http://dx.doi.org/10.1093/humrep/deu198] [PMID: 25104855]
[5]
Ndefo UA, Eaton A, Green MR. Polycystic ovary syndrome: A review of treatment options with a focus on pharmacological approaches. P&T 2013; 38(6): 336-55.
[PMID: 23946629]
[6]
Das V. An introduction to pain pathways and pain “targets”. Prog Mol Biol Transl Sci 2015; 131: 1-30.
[http://dx.doi.org/10.1016/bs.pmbts.2015.01.003] [PMID: 25744668]
[7]
Walters KA, Allan CM, Handelsman DJ. Rodent models for human polycystic ovary syndrome. Biol Reprod 2012; 86(5): 149-, 1-2.
[http://dx.doi.org/10.1095/biolreprod.111.097808] [PMID: 22337333]
[8]
Walters KA. Role of androgens in normal and pathological ovarian function. Reproduction 2015; 149(4): R193-218.
[http://dx.doi.org/10.1530/REP-14-0517] [PMID: 25516989]
[9]
Shi D, Vine DF. Animal models of polycystic ovary syndrome: A focused review of rodent models in relationship to clinical phenotypes and cardiometabolic risk. Fertil Steril 2012; 98(1): 185-193.e2.
[http://dx.doi.org/10.1016/j.fertnstert.2012.04.006] [PMID: 22607890]
[10]
Mannerås L, Cajander S, Holmäng A, et al. A new rat model exhibiting both ovarian and metabolic characteristics of polycystic ovary syndrome. Endocrinology 2007; 148(8): 3781-91.
[http://dx.doi.org/10.1210/en.2007-0168] [PMID: 17495003]
[11]
Maliqueo M, Benrick A, Stener-Victorin E. Rodent models of polycystic ovary syndrome: phenotypic presentation, pathophysiology, and the effects of different interventions. Semin Reprod Med 2014; 32(3): 183-93.
[http://dx.doi.org/10.1055/s-0034-1371090] [PMID: 24715513]
[12]
Divyashree S, Janhavi P, Ravindra PV, Muthukumar SP. Experimental models of polycystic ovary syndrome: An update. Life Sci 2019; 237(237): 116911.
[http://dx.doi.org/10.1016/j.lfs.2019.116911] [PMID: 31606385]
[13]
Paixão L, Ramos RB, Lavarda A, Morsh DM, Spritzer PM. Animal models of hyperandrogenism and ovarian morphology changes as features of polycystic ovary syndrome: a systematic review. Reprod Biol Endocrinol 2017; 15(1): 12.
[http://dx.doi.org/10.1186/s12958-017-0231-z] [PMID: 28183310]
[14]
Roy S, Mahesh VB, Greenblatt RB. Effect of dehydroepiandrosterone and δ4-androstenedione on the reproductive organs of female rats: production of cystic changes in the ovary. Nature 1962; 196(4849): 42-3.
[http://dx.doi.org/10.1038/196042a0] [PMID: 13982862]
[15]
Lee MT, Anderson E, Lee GY. Changes in ovarian morphology and serum hormones in the rat after treatment with dehydroepiandrosterone. Anat Rec 1991; 231(2): 185-92.
[http://dx.doi.org/10.1002/ar.1092310206] [PMID: 1836118]
[16]
Anderson E, Lee MT, Lee GY. Cystogenesis of the ovarian antral follicle of the rat: Ultrastructural changes and hormonal profile following the administration of dehydroepiandrosterone. Anat Rec 1992; 234(3): 359-82.
[http://dx.doi.org/10.1002/ar.1092340307] [PMID: 1443664]
[17]
Lee MJ, Jang M, Bae CS, et al. Effects of oriental medicine Kyung-Ok-Ko on uterine abnormality in hyperandrogenized rats. Rejuvenation Res 2016; 19(6): 456-66.
[http://dx.doi.org/10.1089/rej.2015.1787] [PMID: 26899592]
[18]
Wu G, Hu X, Ding J, Yang J. The effect of glutamine on Dehydroepiandrosterone-induced polycystic ovary syndrome rats. J Ovarian Res 2020; 13(1): 57.
[http://dx.doi.org/10.1186/s13048-020-00650-7] [PMID: 32386521]
[19]
Shen HR, Xu X, Ye D, Li XL. Berberine improves the symptoms of DHEA-induced PCOS rats by regulating gut microbiotas and metabolites. Gynecol Obstet Invest 2021; 86(4): 388-97.
[http://dx.doi.org/10.1159/000518040] [PMID: 34515131]
[20]
Nassar A, Khachab M, Zaatiti H, Kanaan A. Magnolia officinalis ameliorates dehydroepiandrosterone-induced polycystic ovary syndrome in rats. Jundishapur J Nat Pharm Prod 2021; 16(3): e106447.
[http://dx.doi.org/10.5812/jjnpp.106447]
[21]
Çelik LS, Kuyucu Y, Yenilmez ED, Tuli A. Dağlıoğlu K, Mete UÖ. Effects of vitamin D on ovary in DHEA-treated PCOS rat model: A light and electron microscopic study. Ultrastruct Pathol 2018; 42(1): 55-64.
[http://dx.doi.org/10.1080/01913123.2017.1385668] [PMID: 29192811]
[22]
Choi JH, Jang M, Kim EJ, et al. Korean red ginseng alleviates dehydroepiandrosterone-induced polycystic ovarian syndrome in rats via its antiinflammatory and antioxidant activities. J Ginseng Res 2020; 44(6): 790-8.
[http://dx.doi.org/10.1016/j.jgr.2019.08.007] [PMID: 33192122]
[23]
Johansson J, Feng Y, Shao R, Lönn M, Billig H, Stener-Victorin E. Intense electroacupuncture normalizes insulin sensitivity, increases muscle GLUT4 content, and improves lipid profile in a rat model of polycystic ovary syndrome. Am J Physiol Endocrinol Metab 2010; 299(4): E551-9.
[http://dx.doi.org/10.1152/ajpendo.00323.2010] [PMID: 20663984]
[24]
Benrick A, Maliqueo M, Miao S, et al. Resveratrol is not as effective as physical exercise for improving reproductive and metabolic functions in rats with dihydrotestosterone-induced polycystic ovary syndrome. Evid Based Complement Alternat Med 2013; 2013: 1-13.
[http://dx.doi.org/10.1155/2013/964070] [PMID: 23690868]
[25]
Gao Z, Ma X, Liu J, et al. Troxerutin protects against DHT-induced polycystic ovary syndrome in rats. J Ovarian Res 2020; 13(106): 1-11.
[http://dx.doi.org/10.1186/s13048-020-00701-z] [PMID: 32921318]
[26]
Hurliman AK, Osol G, Casson PR, Maille N. Metformin treatment prevents the development of endothelial dysfunction in a rat model of polycystic ovary syndrome (PCOS). Fertil Steril 2012; 98(3): S60.
[http://dx.doi.org/10.1016/j.fertnstert.2012.07.213]
[27]
Jin S, Yuan K, Li M, Xing Y, Jin X. Establishment of a model of dihydrotestosterone-induced polycystic ovary syndrome complicated with atherosclerosis in rats. Zhongguo Jiceng Yiyao 2018; 2(12): 1361-4.
[28]
Ressler IB, Grayson BE, Ulrich-Lai YM, Seeley RJ. Diet-induced obesity exacerbates metabolic and behavioral effects of polycystic ovary syndrome in a rodent model. Am J Physiol Endocrinol Metab 2015; 308(12): E1076-84.
[http://dx.doi.org/10.1152/ajpendo.00182.2014] [PMID: 26078189]
[29]
Zhang F, Ma T, Cui P, et al. Diversity of the gut microbiota in dihydrotestosterone-induced PCOS rats and the pharmacologic effects of diane-35, probiotics, and berberine. Front Microbiol 2019; 10(175): 175.
[http://dx.doi.org/10.3389/fmicb.2019.00175] [PMID: 30800111]
[30]
Barzegar MH, Khazali H, Khazali H, Kalantar SM. Effect of Citrullus colocynthis hydro-alcoholic extract on hormonal and folliculogenesis process in estradiol valerate-induced PCOs rats model: An experimental study. Int J Reprod Biomed 2017; 15(10): 661-8.
[http://dx.doi.org/10.29252/ijrm.15.10.9] [PMID: 29387832]
[31]
Sudhakar P, Suganeswari M, Pushkalai PS, Haripriya S. Regulation of estrous cycle using combination of Gymnema sylyestre and Pergularia daemia in estradiol valerate induced PCOS rats. Asian J Res Pharm Sci 2018; 8(1): 4-8.
[http://dx.doi.org/10.5958/2231-5659.2018.00002.4]
[32]
Shirooie S, Khaledi E, Dehpour AR, et al. The effect of dapsone in testosterone enanthate-induced polycystic ovary syndrome in rat. J Steroid Biochem Mol Biol 2021; 214: 105977.
[http://dx.doi.org/10.1016/j.jsbmb.2021.105977] [PMID: 34428594]
[33]
Karateke A, Dokuyucu R, Dogan H, et al. Investigation of therapeutic effects of erdosteine on polycystic ovary syndrome in a rat model. Med Princ Pract 2018; 27(6): 515-22.
[http://dx.doi.org/10.1159/000494300] [PMID: 30293079]
[34]
Abtahi-Eivari SH, Moghimian M, Soltani M, et al. The effect of galega officinalis on hormonal and metabolic profile in a rat model of polycystic ovary syndrome. Int J Women’s Health Reprod Sci 2017; 6(3): 276-82.
[http://dx.doi.org/10.15296/ijwhr.2018.46]
[35]
Kausar F, Rather MA, Bashir SM, et al. Ameliorative effects of Cuscuta reflexa and Peucedanum grande on letrozole induced polycystic ovary syndrome in Wistar rats. Redox Rep 2021; 26(1): 94-104.
[http://dx.doi.org/10.1080/13510002.2021.1927396] [PMID: 34018905]
[36]
Brawer JR, Munoz M, Farookhi R. Development of the polycystic ovarian condition (PCO) in the estradiol valerate-treated rat. Biol Reprod 1986; 35(3): 647-55.
[http://dx.doi.org/10.1095/biolreprod35.3.647] [PMID: 3098314]
[37]
Linares R, Hernández D, Morán C, et al. Unilateral or bilateral vagotomy induces ovulation in both ovaries of rats with polycystic ovarian syndrome. Reprod Biol Endocrinol 2013; 11(1): 68.
[http://dx.doi.org/10.1186/1477-7827-11-68] [PMID: 23866168]
[38]
Mesbah F, Moslem M, Vojdani Z, Mirkhani H. Does metformin improve in vitro maturation and ultrastructure of oocytes retrieved from estradiol valerate polycystic ovary syndrome-induced rats. J Ovarian Res 2015; 8(1): 74.
[http://dx.doi.org/10.1186/s13048-015-0203-x] [PMID: 26577050]
[39]
Ramalingam K, Pachiappan S, Balasubramanian A. Combined effects of Gymnema sylvestre and Pergularia daemia on letrozole-induced polycystic ovarian syndrome in rats. Asian Pac J Reprod 2021; 10(2): 68-74.
[http://dx.doi.org/10.4103/2305-0500.311610] [http://dx.doi.org/10.4103/2305-0500.311610]
[40]
Abtahi-Eivari SH, Moghimian M, Soltani M, Shoorei H, Hajizadeh H, Shokoohi M. The effect of galega officinalis on hormonal and metabolic profile in a rat model of polycystic ovary syndrome (PCOS). J Med Biol Sci 2019; 6(4): 511-6.
[41]
Jin J, Hu QY, Xu WW, et al. Tanshinone IIA attenuates estradiol induced polycystic ovarian syndrome in mice by ameliorating FSHR expression in the ovary. Exp Ther Med 2019; 17(5): 3501-8.
[http://dx.doi.org/10.3892/etm.2019.7352] [PMID: 30988730]
[42]
Osuka S, Nakanishi N, Murase T, et al. Animal models of polycystic ovary syndrome: A review of hormone‐induced rodent models focused on hypothalamus‐pituitary‐ovary axis and neuropeptides. Reprod Med Biol 2019; 18(2): 151-60.
[http://dx.doi.org/10.1002/rmb2.12262] [PMID: 30996678]
[43]
Kakadia N, Patel P, Deshpande S, Shah G. Effect of Vitex negundo L. seeds in letrozole induced polycystic ovarian syndrome. J Tradit Complement Med 2019; 9(4): 336-45.
[http://dx.doi.org/10.1016/j.jtcme.2018.03.001] [PMID: 31453130]
[44]
Tripathi B, Pandey V, Shukla R, Krishna A. Effect of combined treatment of modern and herbal supplement in the management of letrozole induced polycystic ovary syndrome. J Endocrinol Diabetes 2017; 4(1): 1-8.
[http://dx.doi.org/10.15226/2374-6890/4/1/00171] [http://dx.doi.org/10.15226/2374-6890/4/1/00171]
[45]
Nampoothiri L, Maharjan R, Nagar PS. Effect of Aloe barbadensis Mill. formulation on Letrozole induced polycystic ovarian syndrome rat model. J Ayurveda Integr Med 2010; 1(4): 273-9.
[http://dx.doi.org/10.4103/0975-9476.74090] [PMID: 21731374]
[46]
Sadeghi Ataabadi M, Alaee S, Bagheri MJ, Bahmanpoor S. Role of essential oil of mentha spicata (spearmint) in addressing reverse hormonal and folliculogenesis disturbances in a polycystic ovarian syndrome in a rat model. Adv Pharm Bull 2017; 7(4): 651-4.
[http://dx.doi.org/10.15171/apb.2017.078] [PMID: 29399556]
[47]
Kubatka P, Uramova S, Kello M, et al. Anticancer activities of thymus vulgaris L. in experimental breast carcinoma in vivo and in vitro. Int J Mol Sci 2019; 20(7): 1749.
[http://dx.doi.org/10.3390/ijms20071749] [PMID: 30970626]
[48]
Jiang J, Liang L, Ma Q, Zhao T. Kernel nutrient composition and antioxidant ability of corylus spp. in China. Front Plant Sci 2021; 12: 690966.
[http://dx.doi.org/10.3389/fpls.2021.690966] [PMID: 34249062]
[49]
Jadhav M, Menon S, Shailajan S. Anti-androgenic effect of symploco racemose Roxb. against letrozole induced polycystic ovary using rat model. J Coast Life Med 2013; 1(4): 309-14.
[http://dx.doi.org/10.12980/JCLM.1.2013C79]
[50]
Yang H, Kim HJ, Pyun BJ, Lee HW. Licorice ethanol extract improves symptoms of polycytic ovary syndrome in Letrozole-induced female rats. Integr Med Res 2018; 7(3): 264-70.
[http://dx.doi.org/10.1016/j.imr.2018.05.003] [PMID: 30271715]
[51]
Saiyed A, Jahan N, Makbul SAA, Ansari M, Bano H, Habib SH. Effect of combination of Withania somnifera Dunal and Tribulus terrestris Linn on letrozole induced polycystic ovarian syndrome in rats. Integr Med Res 2016; 5(4): 293-300.
[http://dx.doi.org/10.1016/j.imr.2016.10.002] [PMID: 28462131]
[52]
Liang YJ, Zhang HM, Wu YZ, Hao Q, Wang JD, Hu YL. Inhibiting effect of letrozole combined with curcumin on xenografted endometrial carcinoma growth in nude mice. Chin J Cancer 2010; 29(1): 9-14.
[http://dx.doi.org/10.5732/cjc.009.10440] [PMID: 20038303]
[53]
Nampoothiri LP, Desai BN, Maharjan RH. Aloe barbadensis Mill. formulation restores lipid profile to normal in a letrozole-induced polycystic ovarian syndrome rat model. Pharmacognosy Res 2012; 4(2): 109-15.
[http://dx.doi.org/10.4103/0974-8490.94736] [PMID: 22518083]
[54]
Pyun BJ, Yang H, Sohn E, et al. Tetragonia tetragonioides (pall.) kuntze regulates androgen production in a letrozole-induced polycystic ovary syndrome model. Molecules 2018; 23(5): 1173.
[http://dx.doi.org/10.3390/molecules23051173] [PMID: 29757997]
[55]
Patel R, Shah G. High-fat diet exposure from pre-pubertal age induces polycystic ovary syndrome (PCOS) in rats. Reproduction 2018; 155(2): 139-49.
[http://dx.doi.org/10.1530/REP-17-0584] [PMID: 29196492]
[56]
Begum N, Manipriya K, Veeresh B. Role of high-fat diet on letrozole-induced polycystic ovarian syndrome in rats. Eur J Pharmacol 2022; 917: 174746.
[http://dx.doi.org/10.1016/j.ejphar.2022.174746] [PMID: 34998791]
[57]
Akintayo CO, Johnson AD, Badejogbin OC, et al. High fructose-enriched diet synergistically exacerbates endocrine but not metabolic changes in letrozole-induced polycystic ovarian syndrome in Wistar rats. Heliyon 2021; 7(1): e05890.
[http://dx.doi.org/10.1016/j.heliyon.2020.e05890] [PMID: 33474510]
[58]
Pieczyńska JM, Pruszyńska-Oszmałek E, Kołodziejski PA, Łukomska A, Bajerska J. The role of a high-fat, high-fructose diet on letrozole-induced polycystic ovarian syndrome in prepubertal mice. Nutrients 2022; 14(12): 2478.
[http://dx.doi.org/10.3390/nu14122478] [PMID: 35745209]
[59]
Kumar GS, Tirgar P, Dalal M. Development and evaluation of novel rodent model of PCOS mimicking clinical phenotype in human disease. Middle East Fertil Soc J 2022; 25: 1-13.
[http://dx.doi.org/10.1186/s43043-022-00118-2]
[60]
Patisaul HB, Mabrey N, Adewale HB, Sullivan AW. Soy but not bisphenol A (BPA) induces hallmarks of polycystic ovary syndrome (PCOS) and related metabolic co-morbidities in rats. Reprod Toxicol 2014; 49: 209-18.
[http://dx.doi.org/10.1016/j.reprotox.2014.09.003] [PMID: 25242113]
[61]
Ryu Y, Kim SW, Kim YY, Ku SY. Animal models for human polycystic ovary syndrome (PCOS) focused on the use of indirect hormonal perturbations: A review of the literature. Int J Mol Sci 2019; 20(11): 2720.
[http://dx.doi.org/10.3390/ijms20112720] [PMID: 31163591]
[62]
Akın L, Kendirci M, Narin F, Kurtoğlu S, Hatipoğlu N, Elmalı F. Endocrine disruptors and polycystic ovary syndrome: Phthalates. J Clin Res Pediatr Endocrinol 2020; 12(4): 393-400.
[http://dx.doi.org/10.4274/jcrpe.galenos.2020.2020.0037] [PMID: 32431137]
[63]
Bernuci MP, Szawka RE, Helena CVV, Leite CM, Lara HE, Anselmo-Franci JA. Locus coeruleus mediates cold stress-induced polycystic ovary in rats. Endocrinology 2008; 149(6): 2907-16.
[http://dx.doi.org/10.1210/en.2007-1254] [PMID: 18308852]
[64]
Ellis JM, Li LO, Wu PC, et al. Adipose acyl-CoA synthetase-1 directs fatty acids toward beta-oxidation and is required for cold thermogenesis. Cell Metab 2010; 12(1): 53-64.
[http://dx.doi.org/10.1016/j.cmet.2010.05.012] [PMID: 20620995]
[65]
Salehi MS, Tamadon A, Jafarzadeh Shirazi MR, Namavar MR, Zamiri MJ. The role of arginine-phenylalanine-amide-related peptides in mammalian reproduction. Int J Fertil Steril 2015; 9(3): 268-76.
[PMID: 26644848]
[66]
Lombardi LA, Simões RS, Maganhin CC, et al. Immunohistochemical evaluation of proliferation, apoptosis and steroidogenic enzymes in the ovary of rats with polycystic ovary. Rev Assoc Med Bras 2014; 60(4): 349-56.
[http://dx.doi.org/10.1590/1806-9282.60.04.0014] [PMID: 25211419]
[67]
Pung YF, Chilian WM, Bennett MR, Figg N, Kamarulzaman MH. The JCR:LA-cp rat: A novel rodent model of cystic medial necrosis. Am J Physiol Heart Circ Physiol 2017; 312(3): H541-5.
[http://dx.doi.org/10.1152/ajpheart.00653.2016] [PMID: 27986661]
[68]
Hoo JY, Kumari Y, Shaikh MF, Hue SM, Goh BH. Zebrafish: A versatile animal model for fertility research. BioMed Res Int 2016; 2016(9732780): 1-20.
[http://dx.doi.org/10.1155/2016/9732780] [PMID: 27556045]
[69]
(a) Xu N, Chua AK, Jiang H, Liu NA, Goodarzi MO. Early embryonic androgen exposure induces transgenerational epigenetic and metabolic changes. Mol Endocrinol 2014; 28(8): 1329-36.
[http://dx.doi.org/10.1210/me.2014-1042] [PMID: 24992182];
(b) Armstrong AR. Drosophila melanogaster as a model for nutrient regulation of ovarian function. Reproduction 2020; 159(2): R69-82.
[http://dx.doi.org/10.1530/REP-18-0593] [PMID: 31491744]
[70]
Cai Z, He S, Li T, Zhao L, Zhang K. Plumbagin inhibits proliferation and promotes apoptosis of ovarian granulosa cells in polycystic ovary syndrome by inactivating PI3K/Akt/mTOR pathway. Anim Cells Syst 2020; 24(4): 197-204.
[http://dx.doi.org/10.1080/19768354.2020.1790416] [PMID: 33029296]
[71]
Gao Y, Chen J, Ji R, Ding J, Zhang Y, Yang J. USP25 regulates the proliferation and apoptosis of ovarian granulosa cells in polycystic ovary syndrome by modulating the PI3K/AKT pathway via deubiquitinating PTEN. Front Cell Dev Biol 2021; 9(779718): 779718.
[http://dx.doi.org/10.3389/fcell.2021.779718] [PMID: 34805185]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy