ABSTRACT
Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in women of reproductive age. Obesity, dyslipidemia, impaired glucose tolerance and type 2 diabetes are important clinical problems in patients with PCOS. Furthermore, PCOS is a significant risk factor for cardiovascular diseases and endometrial cancer in the long term. Although a number of genetic and environmental factors have been reported in the development, the underlying pathophysiological mechanism remains unclear. In PCOS, which has an active field of research in gynecology, the lack of consensus on the diagnostic criteria leads to be published of contradictory publications on such a frequent systemic disorder. For this reason, it is very important to reveal the exact pathogenesis of the disease with animal models. The purpose of this review is to summarize the experimental models used to induce PCOS. It has been observed that classical polycystic ovarian morphology can be formed in these ovaries by experimental methods and many hormonal imbalances observed in PCOS were noticed.
Keywords:
Polycystic Ovary syndrome, animal experiment, animal models, gonadal hormones
References
1
March WA, Moore VM, Willson KJ, Phillips DI, Norman RJ, Davies MJ. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod 2010;25:544-51.
2
Sanchón R, Gambineri A, Alpañés M, Martínez-García MÁ, Pasquali R, Escobar-Morreale HF. Prevalence of functional disorders of androgen excess in unselected premenopausal women: a study in blood donors. Hum Reprod 2012;27:1209-16.
3
Stein IF, Leventhal M. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 1935;29:181-91.
4
Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004;81:19-25.
5
Agacayak E, Tunc SY, Sak S, Basaranoglu S, Yüksel H, Turgut A, et al. Levels of Neopterin and other Inflammatory Markers in Obese and Non-Obese Patients with Polycystic Ovary Syndrome. Med Sci Monit 2015;21:2446-55.
6
Homburg R. Pregnancy complications in PCOS. Best Pract Res Clin Endocrinol Metab 2006;20:281-92.
7
Alvarez-Blasco F, Botella-Carretero JI, San Millán JL, Escobar-Morreale HF. Prevalence and characteristics of the polycystic ovary syndrome in overweight and obese women. Arch Intern Med 2006;166:2081-6.
8
Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997;18:774-800.
9
Salley KE, Wickham EP, Cheang KI, Essah PA, Karjane NW, Nestler JE. Glucose intolerance in polycystic ovary syndrome--a position statement of the Androgen Excess Society. J Clin Endocrinol Metab 2007;92:4546-56.
10
Wild RA, Carmina E, Diamanti-Kandarakis E, Dokras A, Escobar-Morreale HF, Futterweit W, et al. Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society. J Clin Endocrinol Metab 2010;95:2038-49.
11
Vgontzas AN, Legro RS, Bixler EO, Grayev A, Kales A, Chrousos GP. Polycystic ovary syndrome is associated with obstructive sleep apnea and daytime sleepiness: role of insulin resistance. J Clin Endocrinol Metab 2001;86:517-20.
12
Berni TR, Morgan CL, Berni ER, Rees DA. Polycystic ovary syndrome is associated with adverse mental health and neurodevelopmental outcomes. J Clin Endocrinol Metab 2018;103:2116-25.
13
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.
14
ROY S, MAHESH VB, GREENBLATT RB. Effect of dehydroepiandrosterone and delta4-androstenedione on the reproductive organs of female rats: production of cystic changes in the ovary. Nature 1962;196:42-3.
15
Ward RC, Costoff A, Mahesh VB. The induction of polycystic ovaries in mature cycling rats by the administration of dehydroepiandrosterone (DHA). Biol Reprod 1978;18:614-23.
16
Lara HE, Ferruz JL, Luza S, Bustamante DA, Borges Y, Ojeda SR. Activation of ovarian sympathetic nerves in polycystic ovary syndrome. Endocrinology 1993;133:2690-5.
17
Abbott DH, Dumesic DA, Eisner JR, Colman RJ, Kemnitz JW. Insights into the development of polycystic ovary syndrome (PCOS) from studies of prenatally androgenized female rhesus monkeys. Trends Endocrinol Metab 1998;9:62-7.
18
Abbott DH, Barnett DK, Bruns CM, Dumesic DA. Androgen excess fetal programming of female reproduction: a developmental aetiology for polycystic ovary syndrome? Hum Reprod Update 2005;11:357-74.
19
Kafali H, Iriadam M, Ozardali I, Demir N. Letrozole-induced polycystic ovaries in the rat: a new model for cystic ovarian disease. Arch Med Res 2004;35:103-8.
20
Fink G. Oestrogen and progesterone interactions in the control of gonadotrophin and prolactin secretion. J Steroid Biochem 1988;30:169-78.
21
Luchetti CG, Solano ME, Sander V, Arcos ML, Gonzalez C, Di Girolamo G, et al. Effects of dehydroepiandrosterone on ovarian cystogenesis and immune function. J Reprod Immunol 2004;64:59-74.
22
Rosa-E-Silva A, Guimaraes MA, Padmanabhan V, Lara HE. Prepubertal administration of estradiol valerate disrupts cyclicity and leads to cystic ovarian morphology during adult life in the rat: role of sympathetic innervation. Endocrinology 2003;144:4289-97.
23
Stikkelbroeck NM, Hermus AR, Braat DD, Otten BJ. Fertility in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Obstet Gynecol Surv 2003;58:275-84.
24
Barnes RB, Rosenfield RL, Ehrmann DA, Cara JF, Cuttler L, Levitsky LL, et al. Ovarian hyperandrogynism as a result of congenital adrenal virilizing disorders: evidence for perinatal masculinization of neuroendocrine function in women. J Clin Endocrinol Metab 1994;79:1328-33.
25
Phocas I, Chryssikopoulos A, Sarandakou A, Rizos D, Trakakis E. A contribution to the classification of cases of non-classic 21-hydroxylase-deficient congenital adrenal hyperplasia. Gynecol Endocrinol 1995;9:229-38.
26
Widdowson EM, McCance RA. A review: new thoughts on growth. Pediatr Res 1975;9:154-6.
27
Foecking EM, McDevitt MA, Acosta-Martínez M, Horton TH, Levine JE. Neuroendocrine consequences of androgen excess in female rodents. Horm Behav 2008;53:673-92.
28
Wu XY, Li ZL, Wu CY, Liu YM, Lin H, Wang SH, et al. Endocrine traits of polycystic ovary syndrome in prenatally androgenized female Sprague-Dawley rats. Endocr J 2010;57:201-9.
29
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;37:830-9.
30
Zurvarra FM, Salvetti NR, Mason JI, Velazquez MM, Alfaro NS, Ortega HH. Disruption in the expression and immunolocalisation of steroid receptors and steroidogenic enzymes in letrozole-induced polycystic ovaries in rat. Reprod Fertil Dev 2009;21:827-39.
31
Mannerås L, Cajander S, Holmäng A, Seleskovic Z, Lystig T, Lönn M, et al. A new rat model exhibiting both ovarian and metabolic characteristics of polycystic ovary syndrome. Endocrinology 2007;148:3781-91.
32
Baulieu EE. The antisteroid RU486 its cellular and molecular mode of action. Trends Endocrinol Metab 1991;2:233-9.
33
Sánchez-Criado JE, Sánchez A, Ruiz A, Gaytán F. Endocrine and morphological features of cystic ovarian condition in antiprogesterone RU486-treated rats. Acta Endocrinol (Copenh) 1993;129:237-45.
34
Zhou H, Ohno N, Terada N, Saitoh S, Naito I, Ohno S. Permselectivity of blood follicle barriers in mouse ovaries of the mifepristone-induced polycystic ovary model revealed by in vivo cryotechnique. Reproduction 2008;136:599-610.
35
Ruiz A, Aguilar R, Tébar AM, 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;55:1284-91.
36
Sánchez-Criado JE, Tébar M, Sánchez A, Gaytán F. Evidence that androgens are involved in atresia and anovulation induced by antiprogesterone RU486 in rats. J Reprod Fertil 1993;99:173-9.
37
Ruiz A, Tébar M, Pérez-Romero A, Rol de Lama MA, Sánchez-Criado JE. Serum levels of GH, IGF-I, LH and ovarian steroids in cyclic and RU486-treated rats. J Endocrinol Invest 1997;20:611-5.
38
Lakhani K, Yang W, Dooley A, El-Mahdi E, Sundaresan M, McLellan S, et al. Aortic function is compromised in a rat model of polycystic ovary syndrome. Hum Reprod 2006;21:651-6.
39
Bernuci MP, Szawka RE, Helena CV, Leite CM, Lara HE, Anselmo-Franci JA. Locus coeruleus mediates cold stress-induced polycystic ovary in rats. Endocrinology 2008;149:2907-16.
40
Baldissera SF, Motta LD, Almeida MC, Antunes-Rodrigues J. Proposal of an experimental model for the study of polycystic ovaries. Braz J Med Biol Res 1991;24:747-51.