Melatoninin Polikistik Over Sendromunda Tuba Uterinadaki Koruyucu Etkisi: Histolojik Çalışma

Abstract

Polikistik over sendromu (PKOS), üreme sağlığını olumsuz etkileyen endokrin ve metabolik bir hastalıktır ve uygulanan destek tedavileri arasında antioksidanların kullanımı da yaygınlaşmaktadır. Çalışmamızda, deneysel PKOS modeli oluşturduğumuz sıçanların döllenme ve gamet taşınımı için kilit rol oynayan tuba uterina dokularında PKOS’un meydana getirebileceği olası değişimleri ve bu değişimler üzerinde ekzojen olarak uygulanan melatoninin koruyucu etkisinin incelenmesi amaçlandı. 6-8 haftalık Sprague dawley cinsi 32 adet dişi sıçan Sham Kontrol Grubu (%1 CMC/gün/gavaj), Melatonin Grubu (2 mg/kg/gün/subkutan), Deneysel PKOS Grubu (%1 CMC içerisinde çözünmüş 1 mg/kg Letrozol/gün/gavaj) ve Deneysel PKOS+Melatonin Grubu (1 mg/kg Letrozol/gün/gavaj+2 mg/kg melatonin/gün/subkutan) olmak üzere 4 gruba ayrıldı. 21 günlük deney bitiminde alınan tuba uterina doku örnekleri Hematoksilen-Eozin boyaması ile incelendi, dokuların epitel ve tüm duvar kalınlıkları ölçülerek, istatistiksel veriler hazırlandı. Deneysel PKOS modeli oluşturulmuş sıçanlarda, sendromun tuba uterina dokusunda kinosilyum ve epitelin de dahil olduğu çeşitli dejenerasyonlara yol açtığı ve epitelde proliferasyona sebep olduğu tespit edildi. Protektif melatonin uygulanmasının ise dejenerasyonları önemli ölçüde engellediği görüldü. Deneysel PKOS olgularında ekzojen melatonin uygulamasının tuba uterinada koruma amaçlı kullanılabileceği kanısına varıldı.

Keywords

• Polikistik Over Sendromu,Tuba Uterina,Melatonin,Sıçan

The Protective Effect of Melatonin on Uterine Tube in Polycystic Ovary Syndrome: Histological Study

Abstract

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder that affects reproductive health adversely. The use of antioxidants become widespread among treatments. We aimed to investigate the possible changes of uterine tube which play a key role in the gamete transport and fertilization, in the experimental PCOS model and also the protective effects of exogenous-applied melatonin on these changes. 6-8 weeks, 32 Sprague Dawley female rats were divided 4 equal groups: Sham Control Group (%1 CMC/day/gavage), Melatonin Group (2 mg/kg/day/subcutaneously), Experimental PCOS Group (1 mg/kg Letrozole [Dissolved in %1 CMC]/day/gavage) and Experimental PCOS+Melatonin Group (1mg/kg Letrozole [Dissolved in %1 CMC]/day/gavage + 2 mg/kg/day/subcutaneously). After the 21 days experiment, uterine tube tissues were taken and examined with Hematoxylin-Eosine. Statistical data were prepared by measuring epithelial height and the wall thickness of the tissues. Kinocilium, epithelium degenerations and epithelium proliferation were seen in uterine tube in the experimental PCOS model. It was observed that protectively applied melatonin inhibited these degenerations significiantly. Exogenous melatonin administration could be used for protection the uterine tube against experimental PCOS.

Keywords

• Polycystic Ovary Syndrome,Uterine Tube,Melatonin,Rat

References

1. 1. Cooney LG, Dokras A. Beyond fertility: Polycystic ovary syndrome and long-term health. Fertility and Sterility 2018; 110(5): 794-809.
2. 2. Dumesic DA, Oberfield SE, Stener-Victorin E, Marhall JC, Laven JS, Legro RS. Scientific statement on the diagnostic criteria, epidemiology, pathophysiology, and molecular genetics of polycystic ovary syndome. Endocrine Reviews 2015; 36(5): 487-525.
3. 3. King AE, Critchley HO. Oestrogen and progesterone regulation of inflammatory processes in the human endometrium. J Steroid Biochem Mol Biol 2010; 120(2–3):116–26.
4. 4. RotterdamESHRE/ASRM-Sponsored PCOS consensusworkshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004; 19(1):41–7.
5. 5. 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 Medicine 2010; 8:41.
6. 6. Baracat MCP, Serafini PC, Simones RS, Maciel GAR, Soares JMS, Baracat EC. Systematic review of cell adhesion molecules and estrogen receptor expression in the endometrium of patients with polycystic ovary syndrome. International Journal of Gynecology and Obstetrics, 2015; 129: 1–4.7. Giudice LC. Endometrium in PCOS: Implantation and predisposition to endocrine CA. Best Practice & Research Clinical Endocrinology & Metabolism, 2006; 20(2): 235-244.
7. 8. Olooto WE, Amballi AA, Banjo TA. A review of female infertility; important etiological factors and management. Journal of Microbiology and Biotechnology Research 2012; 2(3): 379-385.
8. 9. Lyons RA, Saridogan E, Djahanbakhch O. The reproductive significance of human fallopian tube cilia. Human Reproduction 2006; 12(4): 363-372.

9. 10. Ezzati M, Djahanbakhch O, Arian S, Carr BR. Tubal transport of gametes and embryos: A reviewof physiology and pathophysiology. J Assist Reprod Genet 2014;31:1337–1347.
10. 11. Schlegel PN, Fauser BC, Carrel DT, Racowsky C. Biennial review of infertility 2013; London, Springer, 1-264.
11. 12. Zhu J, Xu Y, Rashedi AS, Pavone ME, Kim JJ, Woodruff TK, Burdette JE. Human fallopian tube epithelium co-culture with murine ovarian follicles reveals crosstalk in the reproductive cycle. Molecular Human Reproduction 2016; 22(11): 756-767.
12. 13. Raidt J, Werner C, Menchen T, Dougherty GW, et al. Ciliary function and motor protein composition of human fallopian tubes. Human Reproduction 2015; 30(12): 2871-2880.
13. 14. Günalan E, Yaba A, Yılmaz B. The effect of nutrient supplementation in management of polycystic ovary syndrome associated metabolic dysfunctions: A critical review. Journal of the Turkish German Gynecology Assıciation 2018; 19(4): 1-16.
14. 15. Reiter RJ, Tamura H, Tan DX, et al. Melatonin and the circadian system: Contributions to successful femalere production. Fertility and Sterility. 2014;102:321-8.
15. 16. Aluç E. Rat Beyninde Yüksek Doz Radyasyonla Oluşan Akut Hasara Karşı Melatonin ve Diklofenak’ın Koruyucu Etkisi. Uzmanlık Tezi, İnönü Üniversitesi, Malatya 2013; 62s.
16. 17. Reiter RJ. Pineal melatonin: Cell biology of its synthesis and of its physiological interactions. Endocrine Reviews 1999;12:151-180.
17. 18. Baydas G, Özveren F, Akdemir I, Tuzcu M, Yasar A. Learning and memory deficits in rats induced by chronic thinner exposure are reversed by melatonin. Journal of Pineal Research 2005; 39:50-56.
18. 19. Nikmard F, Hosseini E, Bakhtiyari M, Ashrafi M, Amidi F, Aflatoonian R. Effects of melatonin on oocyte maturation in PCOS Mouse model. Animal Science Journal 2017; 88:586-592.
19. 20. Shreeve N, Cagampang F, Sadek K, Tolhurst M, Houldey A, Hill CM, Brook N, Macklon N, Cheong Y. Poor sleep in PCOS; is melatonin the culprit? Human Reproduction 2013; 28(5): 1348-1353.
20. 21. Pai SA, Majumdar AS. Protective effects of melatonin against metabolic and reproductive disturbances in polycystic ovary syndrome in rats. J Pharm Pharmacol 2014; 66(12): 1710-1721.
21. 22. Yücel GN, Take Kaplanoğlu G, Seymen CM. Karanlığın Mucizesi: Melatonin ve ovaryum etkileşimi. Dicle Tıp Dergisi 2018; 45(1): 85-92.
22. 23. Guo Y, Qi Y, Yang X, Zhao L, Wen S, Liu Y, Tang L. Association between Polycystic Ovary Syndrome and Gut Microbiota. PLOS ONE 2016; 11(4):e01553196.
23. 24. Noorafshan A, Ahmadi M, Mesbah SF , Karbalay-Doust S. Stereological study of the effects of letrozole and estradiol valerate treatment on the ovary of rats, Clin Exp Reprod Med 2013; 40(3):115-121.
24. 25. Xia W, Zhang D, Ouyang J, Liang Y, Zhang H, Huang Z, et al. Effects of pelvic endometriosis and adenomyosis on ciliary beat frequency and muscular contractions in the human fallopian tube. Reproductive Biology and Enocrinology 2018; 16:48.
25. 26. Giudice LC. Endometrium in PCOS: Implantation and predisposition to endocrine CA. Best Practice&Research Clinical Endocrinology&Metabolism 2006; 20(2): 235-244.
26. 27. Giudice LC. Elucidating endometrial function in the post-genomic era. Human Reproduction Update 2003; 9: 223–235.
27. 28. Elliott JL, Hosford SL, Demopoulos RI et al. Endometrial adenocarcinoma and polycystic ovary syndrome:risk factors, management, and prognosis. Southern Medical Journal, 2001; 94: 529–531.
28. 29. Cheung AP. Ultrasound and menstrual history in predicting endometrial hyperplasia in polycystic ovary syndrome. Obstetrics and Gynecology, 2001; 98: 325–331.
29. 30. Briceag I, Costache A, Purcarea VL, et al. Fallopian tubes-Literature review of anatomy and etiology in female infertility. Journal of Medicine and Life 2015; 8(2): 129-131.
30. 31. Yan L, Wang A, Chen L, Shang W, Li M, Zhao Y. Expression of apoptosis-related genes in the endometrium of polycystic ovary syndrome patients during the window of implantation. Gene 2012; 506: 350-354.
31. 32. Barron ML. Light exposure, melatonin secretion, and menstrual cycle parameters: An integrative review. Biological Research for Nursing 2007; 9(1): 49-69.
32. 33. Tagliaferri V, Romualdi D, Scarini E, et al. Melatonin treatment may be able to restore menstrual cyclicity in women with PCOS: A pilot study. Reproductive Sciences 2018; 25(2): 269-275.
33. 34. Pai SA, Majumdar AS. Protective effects of melatonin against metabolic and reproductive distrubances in polycystic ovary syndrome in rats. Journal of Pharmacy 2014; 66: 1710-1721.
34. 35. Kim MK, Park EA, Kim HJ, Choi WY, et al. Does supplementation of in-vitro culture medium with melatonin improve IVF outcome in PCOS? Reproductive BioMedicine Online 2013; 26: 22-29.
35. 36. Li C, Shi Y, Wang L, Chen ZJ. Melatonin receptor 1A gene polymorphism associated with polycystic ovary syndrome. Gynecologic and Obstetric Investigation 2011; 72: 130-134.