Chemical Induce Polycystic Ovarian Syndrome-Preclinical Animal Models
Authors
-
Department of Pharmacology, Parul Institute of Pharmacy and Research, Parul University Limda, Vadodara – 391760, Gujarat ,IN
Aakansha Mishra -
Department of Pharmacology, Parul Institute of Pharmacy and Research, Parul University Limda, Vadodara – 391760, Gujarat ,INJagdish Kakadiya
DOI:
https://doi.org/10.18311/ti/2023/v30i4/34636Keywords:
Gonadotropin, Hyperandrogenism, Metabolic Abnormalities, Ovarian Morphology, Polycystic Ovarian Syndrome, Sex Steroid Hormone ProfileAbstract
Polycystic ovarian syndrome is a complex endocrine disturbance that leads to hyperandrogenism, disruption in the functioning of the Hypothalamic-Pituitary-Ovary (HPO) axis and multiple cysts in ovaries. To understand and study different treatment approaches of polycystic ovarian syndrome, there are several chemical-induced animal models available that mimic polycystic ovarian syndrome. These animal models are designed to closely resemble the characteristic symptoms. Polycystic Ovarian Syndrome’s key characteristics are changes in gonadotropin and sex steroid hormone, ovarian morphology, and metabolic characteristics. Direct hormone-regulated animal models are frequently utilized to study PCOS. Rodent animal model is often used which aims to replicate the key feature of human PCOS. Various endocrine-disrupting chemicals also makes a major role in the development of PCOS. In order to bridge the gap between basic research and clinical application in the field of PCOS, PCOS-induced models are essential tools for improving our understanding of the illness and evaluating innovative therapies. The review discusses various animal models used to induced PCOS by various inducers such as aromatase inhibitor inducer (letrozole), androgen excess inducer (dihydrotestosterone, dehydroepiandrosterone, testosterone), estrogen-induced (estradiol valerate), antiprogesterone (mifepristone), monosodium-L-glutamate, bisphenol-A and tributyltin chloride. This article contributed to underlying the current understanding and provides you a complete review that overall covers various aspects, including the impact of chemical-induced models, which also includes changes in the morphology of ovaries, gonadotropin as well as, and alterations in the level of various sex steroid hormone profile. Additionally it explores the metabolic abnormalities caused by various chemical-inducers used to induce PCOS in animal. The objective of this review is to provide a comprehensive review about various chemical inducers which are responsible for the development of PCOS.
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Copyright (c) 2023 Aakansha Mishra, Jagdish Kakadiya
This work is licensed under a Creative Commons Attribution 4.0 International License.
Accepted 2023-09-16
Published 2023-11-03
References
Baldani DP, Skrgatic L, Ougouag R. Polycystic ovary syndrome: An important underrecognized cardiometabolic risk factor in reproductive-age women. Int J Endocrinol. 2015. https://doi.org/10.1155/2015/786362 DOI: https://doi.org/10.1155/2015/786362
Stener-Victorin E, Padmanabhan V, Walters KA, Campbell RE, Benrick A, Giacobini P, Dumesic DA, Abbott DH. Animal models to understand the etiology and pathophysiology of polycystic ovary syndrome. Endocr Rev. 2020; 41(4):1-39. https://doi.org/10.1210/endrev/ bnaa010 DOI: https://doi.org/10.1210/endrev/bnaa010
Mukherjee P, Roy S, Ghosh D, Nandi SK. Role of animal models in biomedical research: A review. Lab Anim Res. 2022; 38(1):18. https://doi.org/10.1186/s42826-022- 00128-1 DOI: https://doi.org/10.1186/s42826-022-00128-1
Witchel SF, Oberfield SE, Peña AS. Polycystic ovary syndrome: Pathophysiology, presentation, and treatment with emphasis on adolescent girls. J Endocr Soc. 2019; 3(8):1545-73. https://doi.org/10.1210/js.2019-00078 DOI: https://doi.org/10.1210/js.2019-00078
Andrade VH, Mata A, Borges RS, Costa-Silva DR, Martins LM, Ferreira PM, Cunha-Nunes LC, Silva BB. Current aspects of Polycystic Ovary Syndrome: A literature review. Rev Assoc Med Bras. 2016; 62:867-71. https://doi. org/10.1590/1806-9282.62.09.867 DOI: https://doi.org/10.1590/1806-9282.62.09.867
Zueff LF, Martins WP, Vieira CS, Ferriani RA. Ultrasonographic and laboratory markers of metabolic and cardiovascular disease risk in obese women with polycystic ovary syndrome. Ultrasound Obstet Gynecol. 2012; 39(3):341-7. https://doi.org/10.1002/uog.10084 DOI: https://doi.org/10.1002/uog.10084
Corbin CJ, Trant JM, Walters KW, Conley AJ. Changes in testosterone metabolism associated with the evolution of placental and gonadal isozymes of porcine aromatase cytochrome P450. Endocrinology. 1999; 140(11):5202-10. https://doi.org/10.1210/endo.140.11.7140 DOI: https://doi.org/10.1210/endo.140.11.7140
Kafali H, Iriadam M, Ozardalı I, Demir N. Letrozoleinduced polycystic ovaries in the rat: A new model for Cystic Ovarian Disease. Arch Med Res. 2004; 35(2):103-8. https://doi.org/10.1016/j.arcmed.2003.10.005 DOI: https://doi.org/10.1016/j.arcmed.2003.10.005
Baravalle C, Salvetti NR, Mira GA, Pezzone N, Ortega HH. Microscopic characterization of follicular structures in letrozole-induced polycystic ovarian syndrome in the rat. Arch Med Res. 2006; 37(7):830-9. https://doi.org/10.1016/j. arcmed.2006.04.006 DOI: https://doi.org/10.1016/j.arcmed.2006.04.006
Manneras L, Cajander S, Holmäng A, Seleskovic Z, Lystig T, Lönn M, Stener- Victorin E. A new rat model exhibiting both ovarian and metabolic characteristics of Polycystic Ovary Syndrome. Endocrinology. 2007; 148(8):3781-91. https://doi.org/10.1210/en.2007-0168
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):185-93. https://doi. org/10.1016/j.fertnstert.2012.04.006 DOI: https://doi.org/10.1016/j.fertnstert.2012.04.006
Xu XL, Deng SL, Lian ZX, Yu K. Estrogen receptors in Polycystic Ovary Syndrome. Cells. 2021; 10(2):459. https:// doi.org/10.3390/cells10020459 DOI: https://doi.org/10.3390/cells10020459
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. https://doi.org/10.1095/biolreprod35.3.647 DOI: https://doi.org/10.1095/biolreprod35.3.647
Daneasa A, Cucolas C, Lenghel LM, Olteanu D, Orasan R, Filip GA. Letrozole vs estradiol valerate induced PCOS in rats: glycemic, oxidative and inflammatory status assessment. Reproduction. 2016; 151(4):401-9. https://doi. org/10.1530/REP-15-0352 DOI: https://doi.org/10.1530/REP-15-0352
Schulster A, Farookhi R, Brawer JR. Polycystic ovarian condition in estradiol valerate-treated rats: spontaneous changes in characteristic endocrine features. Biol Reprod. 1984; 31(3):587-93. https://doi.org/10.1095/ biolreprod31.3.587 DOI: https://doi.org/10.1095/biolreprod31.3.587
Karimzadeh L, Nabiuni M, Sheikholeslami A, Irian S. Bee venom treatment reduced C-reactive protein and improved follicle quality in a rat model of estradiol valerate-induced Polycystic Ovarian Syndrome. J Venom Anim Toxins Inc Trop Dis. 2012; 18:384-92. https://doi.org/10.1590/S1678- 91992012000400006 DOI: https://doi.org/10.1590/S1678-91992012000400006
Stener-Victorin E, Ploj K, Larsson BM, Holmäng A. Rats with steroid-induced polycystic ovaries develop hypertension and increased sympathetic nervous system activity. Reprod Biol Endocrinol. 2005; 3(1):1-0. https://doi. org/10.1186/1477-7827-3-44 DOI: https://doi.org/10.1186/1477-7827-3-44
Chaudhari NK, Nampoothiri LP. Neurotransmitter alteration in a testosterone propionate-induced polycystic ovarian syndrome rat model. Horm Mol Biol Clin Investig. 2017; 29(2):71-7. PMID:27802175. DOI: https://doi.org/10.1515/hmbci-2016-0035
Beloosesky R, Gold R, Almog B, Sasson R, Dantes A, Land-Bracha A, Hirsh L, Itskovitz-Eldor J, Lessing JB, Homburg R, Amsterdam A. Induction of polycystic ovary by testosterone in immature female rats: Modulation of apoptosis and attenuation of glucose/insulin ratio. Int J Mol Med. 2004; 14(2):207-15. https://doi.org/10.3892/ ijmm.14.2.207
Ota H, Fukushima M, Maki M. Endocrinological and histological aspects of the process of polycystic ovary formation in the rat treated with testosterone propionate. Tohoku Jo Exp Med. 1983; 140(2):121-31. https://doi. org/10.1620/tjem.140.121 DOI: https://doi.org/10.1620/tjem.140.121
Yakubu MT, Olawepo FJ, Olayaki LA, Ibrahim OO. Mifepristone (RU486) induces Polycystic Ovarian Syndrome in female Wistar rats with features analogous to humans. J Endocrinol Reprod. 2015; 19(1):40-51. https:// doi.org/10.18519/jer/2015/v19/86061 DOI: https://doi.org/10.18519/jer/2015/v19/86061
Weisberg E, Croxatto HB, Findlay JK, Burger HG, Fraser IS. A randomized study of the effect of mifepristone alone or in conjunction with ethinyl estradiol on ovarian function in women using the etonogestrel-releasing subdermal implant, Implanon. Contraception. 2011; 84(6):600-8. https://doi.org/10.1016/j.contraception.2011.04.008 DOI: https://doi.org/10.1016/j.contraception.2011.04.008
Sánchez-Criado JE, Sánchez A, Ruiz A, Gaytán F. Endocrine and morphological features of cystic ovarian condition in antiprogesterone RU486-treated rats. European J Endocrinol. 1993; 129(3):237-45. https://doi.org/10.1530/ acta.0.1290237 DOI: https://doi.org/10.1530/acta.0.1290237
Ruiz A, Aguilar R, Tébar M, Gaytán F, Sánchez-Criado JE. RU486-treated rats show endocrine and morphological responses to therapies analogous to responses of women with Polycystic Ovary Syndrome treated with similar therapies. Biol Reprod. 1996; 55(6):1284-91. https://doi. org/10.1095/biolreprod55.6.1284 DOI: https://doi.org/10.1095/biolreprod55.6.1284
Seow KM, Ting CH, Huang SW, Ho LT, Juan CC. The use of dehydroepiandrosterone-treated rats is not a good animal model for the study of metabolic abnormalities in Polycystic Ovary Syndrome. Taiwan J Obstet and Gynec. 2018; 57(5):696-704. https://doi.org/10.1016/j.tjog.2018.08.015 DOI: https://doi.org/10.1016/j.tjog.2018.08.015
Koçak S. PCOS Animal Models: An approach induced by dehydroepiandrosterone. Exp Appl Med Sci. 2021; 2(1):136-45. https://doi.org/10.46871/eams.2021.17 DOI: https://doi.org/10.46871/eams.2021.17
Wang YX, Zhu WJ, Xie BG. Expression of PPAR-γ in adipose tissue of rats with polycystic ovary syndrome induced by DHEA. Mol Med Rep. 2014; 9(3):889-93. https://doi.org/10.3892/mmr.2014.1895 DOI: https://doi.org/10.3892/mmr.2014.1895
Anderson E, Lee GY, O’Brien K. Polycystic ovarian condition in the dehydroepiandrosterone‐treated rat model: Hyperandrogenism and the resumption of meiosis are major initial events associated with cystogenesis of antral follicles. The Anat Rec. 1997; 249(1):44-53. https:// doi.org/10.1002/(SICI)1097-0185(199709)249:1<44::AIDAR6> 3.0.CO;2-F DOI: https://doi.org/10.1002/(SICI)1097-0185(199709)249:1<44::AID-AR6>3.0.CO;2-F
Knudsen JF, Costoff A, Mahesh VB. Dehydroepiandrosterone-induced polycystic ovaries and acyclicity in the rat. Fertil Steril. 1975; 26(8):807-17. https:// doi.org/10.1016/S0015-0282(16)41297-5 DOI: https://doi.org/10.1016/S0015-0282(16)41297-5
Manneras L, Cajander S, Holmäng A, Seleskovic Z, Lystig T, Lönn M, Stener-Victorin E. A new rat model exhibiting both ovarian and metabolic characteristics of polycystic ovary syndrome. Endocrinology. 2007; 148(8):3781-91. https://doi.org/10.1210/en.2007-0168 DOI: https://doi.org/10.1210/en.2007-0168
Osuka S, Nakanishi N, Murase T, Nakamura T, Goto M, Iwase A, Kikkawa F. 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. https://doi.org/10.1002/rmb2.12262 DOI: https://doi.org/10.1002/rmb2.12262
Gao Z, Ma X, Liu J, Ge Y, Wang L, Fu P, Liu Z, Yao R, Yan X. Troxerutin protects against DHT-induced polycystic ovary syndrome in rats. J Ovarian Res. 2020; 13:1-1. https://doi. org/10.1186/s13048-020-00701-z DOI: https://doi.org/10.1186/s13048-020-00701-z
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. https://doi.org/10.3390/ ijms20112720 DOI: https://doi.org/10.3390/ijms20112720
Gaspar RS, Benevides RO, Fontelles JL, Vale CC, França LM, Barros Pde T, Paes AM. Reproductive alterations in hyperinsulinemic but normoandrogenic MSG obese female rats. J Endocrinol. 2016; 229(2):61-72. https://doi. org/10.1530/JOE-15-0453 DOI: https://doi.org/10.1530/JOE-15-0453
Benevides RO, Vale CC, Fontelles JL, Franca LM, Teofilo TS, Silva SN, Paes AM, Gaspar RS. Syzygium Cumini (L.) Skeels improves metabolic and ovarian parameters in female obese rats with malfunctioning hypothalamuspituitary- gonadal axis. J Ovarian Res. 2019; 12:1-0. https:// doi.org/10.1186/s13048-019-0490-8 DOI: https://doi.org/10.1186/s13048-019-0490-8
Zhou W, Liu J, Liao L, Han S, Liu J. Effect of bisphenol A on steroid hormone production in rat ovarian theca-interstitial and granulosa cells. Mol and Cell Endocrinol. 2008; 283(1- 2):12-8. https://doi.org/10.1016/j.mce.2007.10.010 DOI: https://doi.org/10.1016/j.mce.2007.10.010
Fernández M, Bourguignon N, Lux-Lantos V, Libertun C. Neonatal exposure to bisphenol a and reproductive and endocrine alterations resembling the polycystic ovarian syndrome in adult rats. Environ Health Perspect. 2010; 118(9):1217-22. https://doi.org/10.1289/ehp.0901257 DOI: https://doi.org/10.1289/ehp.0901257
Kechagias KS, Semertzidou A, Athanasiou A, Paraskevaidi M, Kyrgiou M. Bisphenol-A and polycystic ovary syndrome: A review of the literature. Rev Environ Heath. 2020; 35(4):323-31. PMID:32663175. https://doi.org/10.1515/ reveh-2020-0032 DOI: https://doi.org/10.1515/reveh-2020-0032
Decherf S, Demeneix BA. The obesogen hypothesis: A shift of focus from the periphery to the hypothalamus. J Toxicol Environ Health, Part B. 2011; 14(5-7):423-48. https://doi. org/10.1080/10937404.2011.578561 DOI: https://doi.org/10.1080/10937404.2011.578561
Merlo E, Silva IV, Cardoso RC, Graceli JB. The obesogen tributyltin induces features of Polycystic Ovary Syndrome (PCOS): A review. J Toxicol Environ Health, Part B. 2018; 21(3):181-206. https://doi.org/10.1080/10937404.2018.149 6214 DOI: https://doi.org/10.1080/10937404.2018.1496214
Shirooie S, Khaledi E, Dehpour AR, Noori T, Khazaei M, Sadeghi F, Sobarzo-Sánchez E. The effect of dapsone in testosterone enanthate-induced Polycystic Ovary Syndrome in rat. J Steroid Biochem Mol Biol. 2021; 214:105977. https://doi.org/10.1016/j.jsbmb.2021.105977 DOI: https://doi.org/10.1016/j.jsbmb.2021.105977
