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HİPERTİROİDİ VE DİYABETİN UTERUSTA VEGF LOKALİZASYONU ÜZERİNE ETKİSİ

Year 2025, Volume: 6 Issue: 3, 405 - 410, 28.11.2025
https://doi.org/10.70813/ssd.1587251

Abstract

Hipertiroidi ve diyabet birbirleri ile ilişkili olabilen endokrin sistem hastalıklardır. Çalışmamızda, deneysel diyabet ve deneysel hipertiroidi oluşturulan ratlardan alınan uterus dokusu üzerinde VEGF ekspresyonun karşılıklı değerlendirilmesi amaçlanmıştır. Çalışmada ağırlıkları yaklaşık 200-220 gram ağırlığında 8-10 haftalık Wistar Albino cinsi erişkin dişi rat kullanıldı. Kontrol, diyabetik ve hipertiroidi olmak üzere üç gruba ayrılan hayvanlar östrus siklusuna göre; östrüs dönemlerinde alındılar. Sıçanlara, deneysel diyabet oluşturmak için 60 mg/kg derişimlerde hazırlanan streptozotosin, intraperitonal yoldan enjekte edildikten 30 gün sonrasında uterus dokuları çıkarıldı. Hayvanlarda hipertiroidi oluşturmak için 21 gün süre ile 250 mcg/kg/gün olmak üzere subkutan enjeksiyon yolu ile tiroksin (L-tiroksin) hormonu enjekte edildi. Doku örnekleri %10 tamponlanmış nötral formalin çözeltisinde tespit edildikten sonra parafin bloklardan 3 µm kalınlığında kesitler alındı. Alınan doku uterus örneklerine VEGF lokalizasyonun belirlenebilmesi için immünohistokimyasal yöntemler uygulandı. Elde edilen dokular karşılaştırılarak değerlendirildi ve uygun alanlardan fotoğraflar çekildi. Kontrol ve deney grupları karşılıklı değerlendirildiğinde diyabetik grupta yer alan uterus dokusunda özellikle, epitel ve stroma alanlarında VEGF lokalizasyonun azalmış olduğu dikkat çekti. Hipertiroidi olan grupta da benzer şekilde kontrol grubundaki VEGF lokalizasyonun deney grubunda azalmış olduğu belirlendi. Dolayısıyla, endokrin hastalıklar olan diyabet ve hipertiroidinin VEGF ekspresyonu üzerinde etkili olduğu ve ekspresyon düzeyinin azalması yönünde katkı sağladığı söylenebilir.

References

  • [1]. Ucer Ozgurel S, Swallow EA, Metzger CE, Allen MR. (2022). Femoral Skeletal Perfusion is Reduced in Male Mice with Type 1 Diabetes. Calcif Tissue Int: Sep;111(3):323-330.
  • [2]. Unver Saraydin S, Özdenoğlu Kutlu B, Saraydin D. (2022). Influence of Diabetes on Morphometric Index of Ovarian Follicles in Streptozocin-Induced Rats. Medical Laboratory Technology Journal: 8(1), 1-11.
  • [3]. Szkudelski T. (2001) The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res: 50:537- 46.
  • [4]. Krassas GE, Poppe K, Glinoer D. (2010). Thyroid function and human reproductive health. Endocrine Reviews, 31 (5):702-755.
  • [5]. Madazlı R, Bulut B, Oncül M, Artar G, Benian A. (2007). Cerrahpaşa Tıp Dergisi, 38:46 – 50.
  • [6]. Groh A, Jahn K, Gröschl M, Hillemacher T, Kornhuber J, Bleich S, Frieling H and Heberlein A. (2019). Short Communication: Interaction of Nerve Growth Factor (NGF) and Vascular Endothelial Growth Factor (VEGF) in Healthy Individuals. Disease Markers: 7510315.
  • [7]. Mercurio A M. (2019). VEGF/Neuropilin Signaling in Cancer Stem Cells. International Journal of Molecular Sciences: 20, 490.
  • [8]. Bao P, Kodra A, Tomic‐Canic M, Golinko MS, Ehrlich HP, Brem H. The role of vascular endothelial growth factor in wound healing. J Surg Res. 2009;153(2):347‐358.
  • [9]. Antonetti D.A., Silva P.S., Stitt A.W. Current understanding of the molecular and cellular pathology of diabetic retinopathy. Nat. Rev. Endocrinol. 2021;17:195–206.
  • [10]. Rehman ZU, Khan J, Noordin S. Diabetic foot ulcers: contemporary assessment and management. J Pak Med Assoc. 2023;73(7):1480‐1487.
  • [11]. Unver Saraydin S, Basol K, Saraydin D. (2023). Determination of VASA and IFITM3 immunolocalization in experimental hyperthyroidism in rat ovaries at the stage of diestrus. AJPCB, 6(1):18-27.
  • [12]. Ozdenoglu B, Unver Saraydin. (2016). Does Diabetes Alter Immunolocalization of Galectin-1 and Galectin-3 in the Rat Ovary? Int. J. Morphol, 34(2):742-751.
  • [13]. Cora MC, Kooistra L, Travlos G. Vaginal Cytology of the Laboratory Rat and Mouse: Review and Criteria for the Staging of the Estrous Cycle Using Stained Vaginal Smears. Toxicol Pathol. 2015;43(6):776-793.
  • [14]. Kaloğlu C, Bulut HE, Hamutoğlu R, Korkmaz EM, Önder O, Dağdeviren T, Aydemir MN. (2020). Wingless ligands and beta-catenin expression in the rat endometrium: The role of Wnt3 and Wnt7a/beta-catenin pathway at the embryo-uterine interface. Mol Reprod Dev: 87(11):1159-1172.
  • [15]. Khursid A, Zardad M, Iftikhar Q. (2009). The prevalence of cutaneous manifestations of diabetes mellitus; J Ayup Coll Abbottabad, 21 (2), 76-79.
  • [16]. Pemayun TG. (2016). Current diagnosis and management of thyroid nodules. Acta Med Indones, 48:247–257.
  • [17]. Surks MI, Ortiz E, Daniels GH, et al. (2004) Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA, 291:228-238.
  • [18]. Mironidou-Tzouveleki M, Tsartsalis S, and Tomos C. (2010). Vascular endothelial growth factor (VEGF) in the pathogenesis of diabetic nephropathy of type 1 diabetes mellitus. Curr Drug Targets, 12, 107-14.
  • [19]. Martin A, Komada MR, and Sane DC. (2003). Abnormal angiogenesis in diabetes mellitus. Med Res Rev, 23, 117-45.
  • [20]. Bhisitkul RB. (2006). Vascular endothelial growth factor biology: clinical implications for ocular treatments. Br J Ophthalmol, 90, 1542-7.
  • [21]. Lineaweaver WC, Lei MP, Mustain W, Oswald TM, Cui D, and Zhang F. (2004). Vascular endothelium growth factor, surgical delay, and skin flap survival. Ann Surg, 239, 866-75.
  • [22]. Lu M, and Adamis AP. (2002). Vascular endothelial growth factor gene regulation and action in diabetic retinopathy. Ophthalmol Clin North Am, 15, 69-79.
  • [23]. Maritim AC, Sanders RA, Watkins JB. (2003). Diabetes, oxidative stress, and antioxidants: a review. Journal of biochemical and molecular toxicology, 17(1), 24–38.
  • [24]. Shima H, Naeem E, Hassan M, Hossein N. (2011). Aloe vera gel protects ovarian structure in diabetic rat. American-Eurasian Journal of Toxicological Sciences, 3(3), 197-203.
  • [25]. Gu CJ, Xie F, Zhang B, Yang HL, Cheng J, He YY, Zhu XY, Li DJ, Li M.Q. (2018). High Glucose Promotes Epithelial-Mesenchymal Transition of Uterus Endometrial Cancer Cells by Increasing ER/GLUT4-Mediated VEGF Secretion. Cellular physiology and biochemistry: international journal of experimental cellular physiology, biochemistry, and pharmacology, 50(2), 706–720.
  • [26]. Kong L, Wei Q, Fedail JS, Shi F, Nagaoka K, Watanabe G. (2015). Effects of thyroid hormones on the antioxidative status in the uterus of young adult rats. The Journal of reproduction and development, 61(3), 219–227.
  • [27]. Mahmud T, Khan QU, Saad S. (2021). The Interplay Between Hyperthyroidism and Ovarian Cytoarchitecture in Albino Rats. Cureus, 13(4).
  • [28]. Aghajanova L, Stavreus-Evers A, Lindeberg M, Landgren BM, Sparre LS, Hovatta O. (2011). Thyroid-stimulating hormone receptor and thyroid hormone receptors are involved in human endometrial physiology. Fertil Steril, 95(1): 230-237.
  • [29]. Bozoglu H, Karaca T. (2015). Oestrogen Receptor Alpha and Progesterone Receptor in Uterus and Ovaries on Different Days of The Oestrus Cycle in Hyperthyroid Rats. Asian JMedSci, 6(4):14-20.
  • [30]. Lutsyk, A, Sogomonian, E. (2012). Structural, functional, and lectin histochemical characteristics of rat ovaries and endometrium in experimental hyper- and hypothyroidism. Folia histochemica et cytobiologica, 50(3), 331–339.
  • [31]. Silva JF, Ocarino M. (2018). Thyroid hormones and female reproduction. Biology of Reproduction, 99(5):907- 921.
  • [32]. Inuwa IM, Williams MA. A. (2006). Morphometric study on the endometrium of rat uterus in hypothyroid and thyroxine treated hypothyroid rats. Ups J Med Sci, 111(2):215- 226.

EFFECT OF HYPERTHYROIDISM AND DIABETES ON VEGF LOCALIZATION IN UTERUS

Year 2025, Volume: 6 Issue: 3, 405 - 410, 28.11.2025
https://doi.org/10.70813/ssd.1587251

Abstract

Hyperthyroidism and diabetes are endocrine system diseases that can be associated with each other. In our study, we aimed to evaluate VEGF expression on uterine tissue taken from experimentally diabetic and experimentally hyperthyroid rats. In the study, 8-10 week old Wistar Albino adult female rats weighing approximately 200-220 grams were used. The animals were divided into three groups as control, diabetic and hyperthyroid, and were taken during the estrous period according to the estrous cycle. In order to create experimental diabetes, streptozotocin prepared at a concentration of 60 mg/kg was injected intraperitoneally into the rats and uterine tissues were removed 30 days later. Thyroxine (L-thyroxine) hormone was injected subcutaneously for 21 days at a dose of 250 mcg/kg/day to create hyperthyroidism in the animals. After the tissue samples were fixed in 10% buffered neutral formalin solution, 3 µm thick sections were taken from paraffin blocks. Immunohistochemical methods were applied to the tissue samples taken to determine VEGF localization. The tissues obtained were compared and evaluated, and photographs were taken from appropriate areas. When the control and experimental groups were evaluated, it was noted that VEGF localization was reduced in the uterine tissue in the diabetic group, especially in the epithelial and stromal areas. Similarly, in the hyperthyroid group, VEGF localization was reduced in the control group and in the experimental group. Therefore, it can be said that diabetes and hyperthyroidism, which are endocrine diseases, have an effect on VEGF expression and contribute to the decrease in expression levels.

References

  • [1]. Ucer Ozgurel S, Swallow EA, Metzger CE, Allen MR. (2022). Femoral Skeletal Perfusion is Reduced in Male Mice with Type 1 Diabetes. Calcif Tissue Int: Sep;111(3):323-330.
  • [2]. Unver Saraydin S, Özdenoğlu Kutlu B, Saraydin D. (2022). Influence of Diabetes on Morphometric Index of Ovarian Follicles in Streptozocin-Induced Rats. Medical Laboratory Technology Journal: 8(1), 1-11.
  • [3]. Szkudelski T. (2001) The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res: 50:537- 46.
  • [4]. Krassas GE, Poppe K, Glinoer D. (2010). Thyroid function and human reproductive health. Endocrine Reviews, 31 (5):702-755.
  • [5]. Madazlı R, Bulut B, Oncül M, Artar G, Benian A. (2007). Cerrahpaşa Tıp Dergisi, 38:46 – 50.
  • [6]. Groh A, Jahn K, Gröschl M, Hillemacher T, Kornhuber J, Bleich S, Frieling H and Heberlein A. (2019). Short Communication: Interaction of Nerve Growth Factor (NGF) and Vascular Endothelial Growth Factor (VEGF) in Healthy Individuals. Disease Markers: 7510315.
  • [7]. Mercurio A M. (2019). VEGF/Neuropilin Signaling in Cancer Stem Cells. International Journal of Molecular Sciences: 20, 490.
  • [8]. Bao P, Kodra A, Tomic‐Canic M, Golinko MS, Ehrlich HP, Brem H. The role of vascular endothelial growth factor in wound healing. J Surg Res. 2009;153(2):347‐358.
  • [9]. Antonetti D.A., Silva P.S., Stitt A.W. Current understanding of the molecular and cellular pathology of diabetic retinopathy. Nat. Rev. Endocrinol. 2021;17:195–206.
  • [10]. Rehman ZU, Khan J, Noordin S. Diabetic foot ulcers: contemporary assessment and management. J Pak Med Assoc. 2023;73(7):1480‐1487.
  • [11]. Unver Saraydin S, Basol K, Saraydin D. (2023). Determination of VASA and IFITM3 immunolocalization in experimental hyperthyroidism in rat ovaries at the stage of diestrus. AJPCB, 6(1):18-27.
  • [12]. Ozdenoglu B, Unver Saraydin. (2016). Does Diabetes Alter Immunolocalization of Galectin-1 and Galectin-3 in the Rat Ovary? Int. J. Morphol, 34(2):742-751.
  • [13]. Cora MC, Kooistra L, Travlos G. Vaginal Cytology of the Laboratory Rat and Mouse: Review and Criteria for the Staging of the Estrous Cycle Using Stained Vaginal Smears. Toxicol Pathol. 2015;43(6):776-793.
  • [14]. Kaloğlu C, Bulut HE, Hamutoğlu R, Korkmaz EM, Önder O, Dağdeviren T, Aydemir MN. (2020). Wingless ligands and beta-catenin expression in the rat endometrium: The role of Wnt3 and Wnt7a/beta-catenin pathway at the embryo-uterine interface. Mol Reprod Dev: 87(11):1159-1172.
  • [15]. Khursid A, Zardad M, Iftikhar Q. (2009). The prevalence of cutaneous manifestations of diabetes mellitus; J Ayup Coll Abbottabad, 21 (2), 76-79.
  • [16]. Pemayun TG. (2016). Current diagnosis and management of thyroid nodules. Acta Med Indones, 48:247–257.
  • [17]. Surks MI, Ortiz E, Daniels GH, et al. (2004) Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA, 291:228-238.
  • [18]. Mironidou-Tzouveleki M, Tsartsalis S, and Tomos C. (2010). Vascular endothelial growth factor (VEGF) in the pathogenesis of diabetic nephropathy of type 1 diabetes mellitus. Curr Drug Targets, 12, 107-14.
  • [19]. Martin A, Komada MR, and Sane DC. (2003). Abnormal angiogenesis in diabetes mellitus. Med Res Rev, 23, 117-45.
  • [20]. Bhisitkul RB. (2006). Vascular endothelial growth factor biology: clinical implications for ocular treatments. Br J Ophthalmol, 90, 1542-7.
  • [21]. Lineaweaver WC, Lei MP, Mustain W, Oswald TM, Cui D, and Zhang F. (2004). Vascular endothelium growth factor, surgical delay, and skin flap survival. Ann Surg, 239, 866-75.
  • [22]. Lu M, and Adamis AP. (2002). Vascular endothelial growth factor gene regulation and action in diabetic retinopathy. Ophthalmol Clin North Am, 15, 69-79.
  • [23]. Maritim AC, Sanders RA, Watkins JB. (2003). Diabetes, oxidative stress, and antioxidants: a review. Journal of biochemical and molecular toxicology, 17(1), 24–38.
  • [24]. Shima H, Naeem E, Hassan M, Hossein N. (2011). Aloe vera gel protects ovarian structure in diabetic rat. American-Eurasian Journal of Toxicological Sciences, 3(3), 197-203.
  • [25]. Gu CJ, Xie F, Zhang B, Yang HL, Cheng J, He YY, Zhu XY, Li DJ, Li M.Q. (2018). High Glucose Promotes Epithelial-Mesenchymal Transition of Uterus Endometrial Cancer Cells by Increasing ER/GLUT4-Mediated VEGF Secretion. Cellular physiology and biochemistry: international journal of experimental cellular physiology, biochemistry, and pharmacology, 50(2), 706–720.
  • [26]. Kong L, Wei Q, Fedail JS, Shi F, Nagaoka K, Watanabe G. (2015). Effects of thyroid hormones on the antioxidative status in the uterus of young adult rats. The Journal of reproduction and development, 61(3), 219–227.
  • [27]. Mahmud T, Khan QU, Saad S. (2021). The Interplay Between Hyperthyroidism and Ovarian Cytoarchitecture in Albino Rats. Cureus, 13(4).
  • [28]. Aghajanova L, Stavreus-Evers A, Lindeberg M, Landgren BM, Sparre LS, Hovatta O. (2011). Thyroid-stimulating hormone receptor and thyroid hormone receptors are involved in human endometrial physiology. Fertil Steril, 95(1): 230-237.
  • [29]. Bozoglu H, Karaca T. (2015). Oestrogen Receptor Alpha and Progesterone Receptor in Uterus and Ovaries on Different Days of The Oestrus Cycle in Hyperthyroid Rats. Asian JMedSci, 6(4):14-20.
  • [30]. Lutsyk, A, Sogomonian, E. (2012). Structural, functional, and lectin histochemical characteristics of rat ovaries and endometrium in experimental hyper- and hypothyroidism. Folia histochemica et cytobiologica, 50(3), 331–339.
  • [31]. Silva JF, Ocarino M. (2018). Thyroid hormones and female reproduction. Biology of Reproduction, 99(5):907- 921.
  • [32]. Inuwa IM, Williams MA. A. (2006). Morphometric study on the endometrium of rat uterus in hypothyroid and thyroxine treated hypothyroid rats. Ups J Med Sci, 111(2):215- 226.
There are 32 citations in total.

Details

Primary Language English
Subjects Clinical Sciences (Other)
Journal Section Research Article
Authors

Berna Özdenoğlu Kutlu 0000-0002-0345-3940

Serpil Ünver Saraydin 0000-0001-7639-7487

Özlem Delibaş 0000-0002-1764-6807

Publication Date November 28, 2025
Submission Date November 18, 2024
Acceptance Date August 7, 2025
Published in Issue Year 2025 Volume: 6 Issue: 3

Cite

APA Özdenoğlu Kutlu, B., Ünver Saraydin, S., & Delibaş, Ö. (2025). EFFECT OF HYPERTHYROIDISM AND DIABETES ON VEGF LOCALIZATION IN UTERUS. Selçuk Sağlık Dergisi, 6(3), 405-410. https://doi.org/10.70813/ssd.1587251