Jinekolojik Rahatsızlıklarda Kullanılan Deneysel Hayvan Modelleri

Yıl 2024, Cilt: 26 Sayı: S1, 72 - 78, 30.06.2024

Mert İlhan

https://doi.org/10.18678/dtfd.1503734

Öz

Bu çalışma kadınların üreme sağlığını etkileyen iki önemli hastalık olan endometriyoz ve polikistik over sendromu (PKOS) için oluşturulan hayvan modellerine odaklanmaktadır. Endometriyozun östrojene bağımlı bir durum olarak karakterize edilmesi, östrojenin hastalığın gelişimi ve tedavi stratejilerinin anlaşılmasındaki rolünü vurgulamaktadır. Sıçan ve fare modelleri, endometriyozun patofizyolojisini anlamak ve yeni tedavi yaklaşımlarını test etmek için çok önemlidir. Bu modeller özellikle hormonların ve bağışıklık sistemi modülatörlerinin endometriyoz üzerindeki etkilerinin değerlendirilmesinde önem arz etmektedir. PKOS'un deneysel modelleri bu durumun gelişiminde hiperandrojenizmin merkezi rolünü vurgulamaktadır. Dehidroepiandrosteron, testosteron propiyonat ve letrozol gibi maddelerin neden olduğu modeller, PKOS ile ilişkili metabolik ve endokrinolojik bozulmalara ilişkin öngörü sağlamaktadır. Özellikle letrozolün neden olduğu model, hormonal dengesizlikler ile PKOS'un başlangıcı arasındaki ilişkinin anlaşılmasına yardımcı olmaktadır. Her iki hastalığın deneysel modelleri, hem bilimsel araştırmalar hem de klinik araştırmalar için kritik bilgiler sunmaktadır. Bu hastalıkların patofizyolojisini anlamak ve yeni tedavi stratejileri geliştirmek için gerekli verileri sağlamaktadır. Bu çalışma, deneysel modellerden elde edilen bulguların kadınların üreme sağlığını nasıl iyileştirebileceğini ve bu hastalıklara yönelik daha etkili tedavilere nasıl yol açabileceğini göstermektedir. Hormonal ve bağışıklık sistemi mekanizmalarının daha iyi anlaşılması gelecekteki araştırmalara yol gösterecek ve bu durumların tedavisi için yenilikçi çözümler sunacaktır.

Anahtar Kelimeler

Jinekolojik rahatsızlıklar, endometriyoz, polikistik over sendromu

Experimental Animal Models in Obstetrics and Gynecology

Öz

This study focuses on two major diseases affecting women's reproductive health: endometriosis and polycystic ovary syndrome (PCOS). Endometriosis is characterized as an estrogen-dependent condition, highlighting estrogen's role in understanding the disease's development and treatment strategies. Rat and mouse models are crucial for comprehending the pathophysiology of endometriosis and testing new therapeutic approaches. These models are particularly valuable in evaluating the effects of hormones and immune system modulators on endometriosis. Conversely, experimental models of PCOS emphasize the central role of hyperandrogenism in the development of this condition. Models induced by substances like dehydroepiandrosterone, testosterone propionate, and letrozole provide insights into the metabolic and endocrinological disruptions associated with PCOS. The letrozole-induced model, in particular, helps in understanding the relationship between hormonal imbalances and the onset of PCOS. Experimental models of both diseases offer critical knowledge for both basic science research and clinical applications. They provide essential data for understanding the pathophysiology of these conditions and developing new treatment strategies. This study demonstrates how findings from experimental models can improve women's reproductive health and lead to more effective treatments for these diseases. An enhanced understanding of hormonal and immune system mechanisms will guide future research and offer innovative solutions for treating these conditions.

Anahtar Kelimeler

Gynecological disorders, endometriosis, polycystic ovary syndrome

Kaynakça

• Dunselman GA, Vermeulen N, Becker C, Calhaz-Jorge C, D'Hooghe T, De Bie B, et al. ESHRE guideline: Management of women with endometriosis. Hum Reprod. 2014;29(3):400-12.
• Vitale SG, La Rosa VL, Rapisarda AMC, Lagana AS. Impact of endometriosis on quality of life and psychological well-being. J Psychosom Obstet Gynaecol. 2017;38(4):317-19.
• Lagana AS, Garzon S, Franchi M, Casarin J, Gullo G, Ghezzi F. Translational animal models for endometriosis research: A long and windy road. Ann Transl Med. 2018;6(22):431.
• Lagana AS, Vitale SG, Salmeri FM, Triolo O, Ban Frangez H, Vrtacnik-Bokal E, et al. Unus pro omnibus, omnes pro uno: A novel, evidence-based, unifying theory for the pathogenesis of endometriosis. Med Hypotheses. 2017;103:10-20.
• Azziz R, Carmina E, Chen Z, Dunaif A, Laven JS, Legro RS, et al. Polycystic ovary syndrome. Nat Rev Dis Primers. 2016;2:16057.
• Sander VA, Hapon MB, Sicaro L, Lombardi EP, Jahn GA, Motta AB. Alterations of folliculogenesis in women with polycystic ovary syndrome. J Steroid Biochem Mol Biol. 2011;124(1-2):58-64.
• Carmina E. Diagnosis of polycystic ovary syndrome: from NIH criteria to ESHRE-ASRM guidelines. Minerva Ginecol. 2004;56(1):1-6.
• 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(1):19-25.
• Koçak S. PCOS animal models: An approach induced by dehydroepiandrosterone. Exp Appl Med Sci. 2021;2(1):136-45.
• Grümmer R. Animal models in endometriosis research. Hum Reprod Update. 2006;12(5):641-9.
• Cummings AM, Metcalf JL, Birnbaum L. Promotion of endometriosis by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats and mice: time-dose dependence and species comparison. Toxicol Appl Pharmacol. 1996;138(1):131-9.
• Vernon MW, Wilson EA. Studies on the surgical induction of endometriosis in the rat. Fertil Steril. 1985;44(5):684-94.
• Katsuki Y, Takano Y, Futamura Y, Shibutani Y, Aoki D, Udagawa Y, et al. Effects of dienogest, a synthetic steroid, on experimental endometriosis in rats. Eur J Endocrinol. 1998;138(2):216-26.
• Somigliana E, Vigano P, Rossi G, Carinelli S, Vignali M, Panina-Bordignon P. Endometrial ability to implant in ectopic sites can be prevented by interleukin-12 in a murine model of endometriosis. Hum Reprod. 1999;14(12):2944-50.
• Hirata T, Osuga Y, Yoshino O, Hirota Y, Harada M, Takemura Y, et al. Development of an experimental model of endometriosis using mice that ubiquitously express green fluorescent protein. Hum Reprod. 2005;20(8):2092-6.
• Yao Z, Shen X, Capodanno I, Donnelly M, Fenyk-Melody J, Hausamann J, et al. Validation of rat endometriosis model by using raloxifene as a positive control for the evaluation of novel SERM compounds. J Invest Surg. 2005;18(4):177-83.
• Rice VM. Conventional medical therapies for endometriosis. Ann N Y Acad Sci. 2002;955:343-52.
• Rossi G, Somigliana E, Moschetta M, Santorsola R, Cozzolino S, Filardo P, et al. Dynamic aspects of endometriosis in a mouse model through analysis of implantation and progression. Arch Gynecol Obstet. 2000;263(3):102-7.
• Schor E, Baracat EC, Simoes MJ, de Freitas V, Giannotti Filho O, de Lima GR. Effects of conjugated estrogens and progestogen in surgically induced endometriosis in oophorectomized rats. Clin Exp Obstet Gynecol. 1999;26(3-4):158-61.
• Fang Z, Yang S, Lydon JP, DeMayo F, Tamura M, Gurates B, et al. Intact progesterone receptors are essential to counteract the proliferative effect of estradiol in a genetically engineered mouse model of endometriosis. Fertil Steril. 2004;82(3):673-8.
• Kudoh M, Susaki Y, Ideyama Y, Nanya T, Mori M, Shikama H. Inhibitory effects of a novel aromatase inhibitor, YM511, on growth of endometrial explants and insulin-like growth factor-I gene expression in rats with experimental endometriosis. J Steroid Biochem Mol Biol. 1997;63(1-3):75-80.
• Sakata M, Terakawa N, Mizutani T, Tanizawa O, Matsumoto K, Terada N, et al. Effects of danazol, gonadotropin-releasing hormone agonist, and a combination of danazol and gonadotropin-releasing hormone agonist on experimental endometriosis. Am J Obstet Gynecol. 1990;163(5 Pt 1):1679-84.
• Jones RC. The effect of a luteinizing hormone releasing hormone (LRH) agonist (Wy-40,972), levonorgestrel, danazol and ovariectomy on experimental endometriosis in the rat. Acta Endocrinol (Copenh). 1984;106(2):282-8.
• Saito T, Yoshizawa M, Yamauchi Y, Kinoshita S, Fujii T, Mieda M, et al. Effects of the novel orally active antiestrogen TZE-5323 on experimental endometriosis. Arzneimittelforschung. 2003;53(7):507-14.
• Yano S, Ikegami Y, Nakao K. Studies on the effect of the new non-steroidal aromatase inhibitor fadrozole hydrochloride in an endometriosis model in rats. Arzneimittelforschung. 1996;46(2):192-5.
• Uchiide I, Ihara T, Sugamata M. Pathological evaluation of the rat endometriosis model. Fertil Steril. 2002;78(4):782-6.
• Ingelmo JM, Quereda F, Acien P. Intraperitoneal and subcutaneous treatment of experimental endometriosis with recombinant human interferon-alpha-2b in a murine model. Fertil Steril. 1999;71(5):907-11.
• Keenan JA, Williams-Boyce PK, Massey PJ, Chen TT, Caudle MR, Bukovsky A. Regression of endometrial explants in a rat model of endometriosis treated with the immune modulators loxoribine and levamisole. Fertil Steril. 1999;72(1):135-41.
• D'Antonio M, Martelli F, Peano S, Papoian R, Borrelli F. Ability of recombinant human TNF binding protein-1 (r-hTBP-1) to inhibit the development of experimentally-induced endometriosis in rats. J Reprod Immunol. 2000;48(2):81-98.
• Nothnick WB, Curry TE, Vernon MW. Immunomodulation of rat endometriotic implant growth and protein production. Am J Reprod Immunol. 1994;31(2-3):151-62.
• Lebovic DI, Kir M, Casey CL. Peroxisome proliferator-activated receptor-gamma induces regression of endometrial explants in a rat model of endometriosis. Fertil Steril. 2004;82(Suppl 3):1008-13.
• Matsuzaki S, Canis M, Darcha C, Dallel R, Okamura K, Mage G. Cyclooxygenase-2 selective inhibitor prevents implantation of eutopic endometrium to ectopic sites in rats. Fertil Steril. 2004;82(6):1609-15.
• Efstathiou JA, Sampson DA, Levine Z, Rohan RM, Zurakowski D, Folkman J, et al. Nonsteroidal antiinflammatory drugs differentially suppress endometriosis in a murine model. Fertil Steril. 2005;83(1):171-81.
• Dinulescu DM, Ince TA, Quade BJ, Shafer SA, Crowley D, Jacks T. Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer. Nat Med. 2005;11(1):63-70.
• Otsuka J, Okuda T, Sekizawa A, Amemiya S, Saito H, Okai T, et al. K-ras mutation may promote carcinogenesis of endometriosis leading to ovarian clear cell carcinoma. Med Electron Microsc. 2004;37(3):188-92.
• Elsheikh A, Milingos S, Loutradis D, Kallipolitis G, Michalas S. Endometriosis and reproductive disorders. Ann N Y Acad Sci. 2003;997:247-54.
• Moon CE, Bertero MC, Curry TE, London SN, Muse KN, Sharpe KL, et al. The presence of luteinized unruptured follicle syndrome and altered folliculogenesis in rats with surgically induced endometriosis. Am J Obstet Gynecol. 1993;169(3):676-82.
• Steinleitner A, Lambert H, Roy S. Immunomodulation with pentoxifylline abrogates macrophage-mediated infertility in an in vivo model: a paradigm for a novel approach to the treatment of endometriosis-associated subfertility. Fertil Steril. 1991;55(1):26-31.
• Steinleitner A, Lambert H, Suarez M, Serpa N, Robin B, Cantor B. Periovulatory calcium channel blockade enhances reproductive performance in an animal model for endometriosis-associated subfertility. Am J Obstet Gynecol. 1991;164(4):949-52.
• Berkley KJ, Dmitrieva N, Curtis KS, Papka RE. Innervation of ectopic endometrium in a rat model of endometriosis. Proc Natl Acad Sci U S A. 2004;101(30):11094-8.
• Berkley KJ, Cason A, Jacobs H, Bradshaw H, Wood E. Vaginal hyperalgesia in a rat model of endometriosis. Neurosci Lett. 2001;306(3):185-8.
• Parker CR Jr, Mahesh VB. Hormonal events surrounding the natural onset of puberty in female rats. Biol Reprod. 1976;14(3):347-53.
• Singh KB. Persistent estrus rat models of polycystic ovary disease: an update. Fertil Steril. 2005;84(Suppl 2):1228-34.
• Apter D, Butzow T, Laughlin GA, Yen SS. Accelerated 24-hour luteinizing hormone pulsatile activity in adolescent girls with ovarian hyperandrogenism: relevance to the developmental phase of polycystic ovarian syndrome. J Clin Endocrinol Metab. 1994;79(1):119-25.
• Haning RV Jr, Hua JJ, Hackett RJ, Wheeler CA, Frishman GN, Seifer DB, et al. Dehydroepiandrosterone sulfate and anovulation increase serum inhibin and affect follicular function during administration of gonadotropins. J Clin Endocrinol Metab. 1994;78(1):145-9.
• 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(2):456-88.
• 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.
• 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.
• Beloosesky R, Gold R, Almog B, Sasson R, Dantes A, Land-Bracha A, et al. 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.
• Carriere PD, Brawer JR, Farookhi R. Pituitary gonadotropin-releasing hormone receptor content in rats with polycystic ovaries. Biol Reprod. 1988;38(3):562-7.
• 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.
• Diamanti-Kandarakis E. Polycystic ovarian syndrome: pathophysiology, molecular aspects and clinical implications. Expert Rev Mol Med. 2008;10:e3.
• Sanchez-Criado JE, Bellido C, Galiot F, Lopez FJ, Gaytan F. A possible dual mechanism of the anovulatory action of antiprogesterone RU486 in the rat. Biol Reprod. 1990;42(5-6):877-86.
• Ajika K, Krulich L, Fawcett CP, McCann SM. Effects of estrogen on plasma and pituitary gonadotropins and prolactin, and on hypothalamic releasing and inhibiting factors. Neuroendocrinology. 1972;9(5):304-15.