Deneysel Oluşturulan Hipertroidi Rat Modelinde Hipertroidi'nin Endometriyum Dokusu Üzerine Histopatolojik Etkilerinin Araştırılması

Abstract

Amaç: Bu çalışmada deneysel olarak dişi ratlarda oluşturulan hipertiroidinin uterus üzerinde meydana getirdiği histopatolojik değişikliklerin incelenmesi amaçlanmıştır. Yöntem: Ağırlıkları 200-220 gr olan yeni erişkin 16 adet Wistar albino dişi rat kullanıldı. Grup 1’e (Kontrol grubu) 25 gün boyunca 3 mL distile su oral yolla verildi, Grup 2’ye 25 gün boyunca 3 mL distile su içinde çözülmüş 100 μg/gün L-thyroxine oral gavaj yoluyla verildi. Uterus dokusu kesitlerinde apoptotik hücre ölümünü tespit etmek için Caspase 3 primer antikoru ile otofajik hücre ölümünü tespit etmek için ise LC3B primer antikoru ile inkübasyon uygulandı. İmmünpozitiflikler değerlendirildi ve histolojik inceleme yapıldı. Bulgular: Apoptotik hücre ölümü açısından her iki grupta da herhangi bir immunpozitiflik görülmedi. Otofajik hücre ölümü açısından gruplar arasında farklılıklara rastlandı. Epitel hücrelerinde bazı yerlerde hiperplazinin olduğu, hücrelerin dejeneratif değişimlere uğradığı gözlendi. Endometriumda ödematöz alanlara ve mononükleer inflamatuar hücre infiltrasyonlarına rastlandı. Sonuç: Hipertiroidinin erişkin rat endometriyumunda ödematöz ve inflamatuar değişikliklere sebep olduğunu, otofajiyi artırdığını gözlemledik. Otofajideki artışın artan inflamasyonun ve bozulan homeostazisin etkisinden kaynaklandığını düşünmekteyiz. Hipertiroidinin doku düzeyindeki etkilerinin araştırıldığı detaylı moleküler çalışmalara ihtiyaç vardır.

Keywords

• Apoptoz
• otofaji
• endometriyum
• deneysel hipertroidi
• rat

Investigation of the Histopathological Effects of Hyperthyroidism on Endometrial Tissue in an Experimental Hyperthyroidism Rat Model

Abstract

Objective: It was aimed to investigate histopathological changes of rat uterus in experimental hyperthyroidism. Methods: 16 new adult Wistar albino female rats weighing 200-220 g were used. Group 1 (Control group) were given 3 ml distilled water for 25 days, Group 2 was given 100 µg/day of L-thyroxine dissolved in 3 mL distilled water by oral gavage for 25 days. In the uterine tissue sections, incubation was performed with the Caspase 3 primary antibody to detect apoptotic cell death and LC3B primary antibody to detect autophagic cell death. Immunositivities were evaluated and histological examination was performed. Results: In terms of apoptotic cell death, no immunopositivity was observed in both group. Differences were found between the groups in terms of autophagic cell death. It was observed that there is hyperplasia in some places in epithelial cells and the cells undergo degenerative changes. In the endometrium, edematous areas and mononuclear inflammatory cell infiltrations were noted. Conclusion: We have observed that hyperthyroidism causes edematous and inflammatory changes in the endometrium of adult rats, increases autophagy. We believe that the increase in autophagy is due to the effect of increased inflammation and impaired homeostasis. Detailed molecular studies are needed to investigate the effects of hyperthyroidism at the tissue level.

Keywords

• Endometrium
• rat
• Apoptosis
• autophagy
• experimental hyperthyroidism

References

1. Kaplan S, Türk A, Aydın H, Erten M, Kırıcı P. Vitamin D improves oxidative stress and histopathological damage in rat ovaries caused by hyperthyroidism. J Obstet Gynaecol Res. 2021;47(10):3551-3560. doi:10.1111/jog.14948.
2. Silva JF, Ocarino M. Thyroid hormones and female reproduction. Biology of Reproduction. 2018;99(May):907-921. doi:10.1093/biolre/ioy115.
3. Bozoglu H, Karaca T. Oestrogen Receptor Alpha and Progesterone Receptor in Uterus and Ovaries on Different Days of The Oestrus Cycle in Hyperthyroid Rats. Asian JMedSci. 2015;6(4):14-20. doi:10.3126/ajms.v6i4.11816.
4. Kowalczyk-Zieba, I.; Staszkiewicz-Chodor, J.; Boruszewska, D.; Lukaszuk, K.; Jaworska, J.; Woclawek-Potocka, I. Hypothyroidism Affects Uterine Function via the Modulation of Prostaglandin Signaling. Animals. 2021; 11, 2636. doi:10.3390/ani11092636.
5. GE Krassas, K Poppe, D Glinoer. Thyroid Function and Human Reproductive Health. Endocrine Reviews. 2010; 31(5) 702–755. doi:10.1210/er.2009-0041.
6. Poppe K, Glinoer D, Steirteghem AV, Tournaye H, Devroey P, Schiettecatte J, et all. Thyroid Dysfunction and Autoimmunity in Infertile Women. Thyroid. 2002;12(11):997-1001. doi:10.1089/105072502320908330.
7. Mahmud T, Khan QU, Saad S. The Interplay Between Hyperthyroidism and Ovarian Cytoarchitecture in Albino Rats. Cureus. 2021;13(4). doi:10.7759/cureus.14517.
8. Zaporozhan V, Mescheryakova N. Hıstopathologıcal Changes In Testıcles And Uterus Of Rats Wıth Hyperthyroıdısm And Hypothyroıdısm. Scripta Scientifica Medica. 2013;45(4):77-83. doi:10.14748/ssm.v45i4.239.

9. Maruyama T, Masuda H, Ono M, Kajitani T, Yoshimura Y. Human uterine stem/progenitor cells: their possible role in uterine physiology and pathology. Reproduction. 2010; 140:11-22. doi:10.1530/REP-09-0438.
10. Lutsyk A, Sogomonian E. Structural, functional, and lectin histochemical characteristics of rat ovaries and endometrium in experimental hyper- and hypothyroidism. Folia Histochem Cytobiol. 2012; 50(3):331-339. doi: 10.5603/19742 .
11. Aghajanova L, Stavreus-Evers A, Lindeberg M, Landgren BM, Sparre LS, Hovatta O. Thyroid-stimulating hormone receptor and thyroid hormone receptors are involved in human endometrial physiology. Fertil Steril. 2011; 95(1): 230-237. doi: 10.1016/j.fertnstert.2010.06.079.
12. Choksi NY, Jahnke GD, Hilaire CS, Shelby M. Role of Thyroid Hormones in Human and Laboratory Animal Reproductive Health. Birth Defect Res B. 2003; 68(6):479-491. doi:10.1002/bdrb.10045.
13. Inuwa IM, Williams MA. A morphometric study on the endometrium of rat uterus in hypothyroid and thyroxine treated hypothyroid rats. Ups J Med Sci. 2006;111(2):215-226. doi:10.3109/2000-1967-042.
14. Wipawee W, Hewitt SC, Orvis GD, Behringer RR, Korach KS. Uterine epithelial estrogen receptor α is dispensable for proliferation but essential for complete biological and biochemical responses. Proc Natl Acad Sci USA. 2010;107(45):19272-19277. doi:10.1073/pnas.1013226107.
15. De Vito P, Incerpi S, Pedersen JZ, Luly P, Davis FB, Davis PJ. Thyroid hormones as modulators of immune activities at the cellular level. Thyroid. 2011;21(8):879-890. doi:10.1089/thy.2010.0429.
16. Morsy MA, Abdelraheem WM, El-Hussieny M, Refaie MMM. Protective effects of irbesartan, an angiotensin receptor blocker with PPARγ agonistic activity, against estradiol benzoate-induced endometrial hyperplasia and atypia in female rats via modulation of TNFα/survivin pathway. Pharmaceuticals. 2021;14(7). doi:10.3390/ph14070649.
17. Freitas ES, Leite ED, Souza CA, Ocarino NM, Ferreira E, Cassali GD, Gomes MG, Serakides R. Histomorphometry and expression of Cdc47 and caspase-3 in hyperthyroid rat uteri and placentas during gestation and postpartum associated with fetal development. Reprod Fertil Dev. 2007;19(3):498-509. doi: 10.1071/rd06086.
18. Yang S, Wang H, Li D, Li M. Role of endometrial autophagy in physiological and pathophysiological processes. J Cancer. 2019;10(15):3459-3471. doi:10.7150/jca.31742.
19. Shen HH, Zhang T, Yang HL, Lai ZZ, Zhou WJ, Mei J, et al. Ovarian hormones-autophagy-immunity axis in menstruation and endometriosis. Theranostics. 2021;11(7):3512-3526. doi:10.7150/THNO.55241.
20. Choi S, Shin H, Song H, Lim HJ. Suppression of autophagic activation in the mouse uterus by estrogen and progesterone. J Endocrinol. 2014;221(1):39-50. doi:10.1530/JOE-13-0449.
21. Zhou S, Zhao L, Yi T, Wei Y, Zhao X. Menopause-induced uterine epithelium atrophy results from arachidonic acid/prostaglandin E2 axis inhibition-mediated autophagic cell death. Sci Rep. 2016;6(August 2015):1-14. doi:10.1038/srep31408.
22. Mancini A, Di Segni C, Raimondo S, et al. Thyroid Hormones, Oxidative Stress, and Inflammation. Mediators Inflamm. 2016;2016:6757154. doi:10.1155/2016/6757154.