HİPOTRİOİD SIÇANLARIN YUMURTALIK FOLLİKÜLLERİNDE EGFR EKSPRESYONU
Year 2026,
Volume: 43 Issue: 1
,
37
-
45
,
01.04.2026
Fatma Betül Silinmez
,
Hülya Çetin
,
İlknur Lafci
,
Semih Tan
,
Saim Özdamar
Abstract
Hipotiroidizm, tiroid hormonlarının (T4 ve T3) yetersiz üretimi sonucu vücut fonksiyonlarının yavaşlamasına neden olur. Aynı zamanda üreme sağlığını da olumsuz etkiler. Nitekim hayvan çalışmaları hipotiroidizmin foliküler olgunlaşmayı engellediğini ve over fonksiyonlarını bozduğunu göstermiştir. Epidermal büyüme faktörü (EGF), hücre büyümesi ve farklılaşmasında hayati rol oynayan bir polipeptittir. Bu çalışmada yetişkin sıçanlarda oluşturulan hipotiroidizmin over folikülleri ve EGFR ekspresyonundaki değişiklikler üzerine etkilerinin araştırılması amaçlanmıştır. Çalışmamızda 18 dişi Wistar sıçanı kullanılmıştır. Rastgele seçilen 10 sıçanın içme suyuna 30 gün boyunca 10 mg/kg metimazol katılarak hipotiroidi grubu oluşturulmuştur. Herhangi bir tedavi uygulanmayan kalan 8 sıçan kontrol grubunu oluşturmuştur. Metimazol ile oluşturulan deneysel hipotiroidizmin over üzerine etkileri biyokimyasal, histopatolojik ve mRNA ekspresyonu değişiklikleri açısından araştırılmıştır. Metimazol verilen sıçanlarda serum T3 düzeylerinde anlamlı düşüş gözlenmiştir. Hipotiroidizm grubundaki sıçanların ortalama vücut ve yumurtalık ağırlıklarının yanı sıra birincil, ikincil ve üçüncül folikül sayılarının da anlamlı derecede azaldığı bulundu. İmmünohistokimyasal olarak, hipotiroidizm grubundaki sıçanlarda EGFR ekspresyonunun da azaldığı bulundu. RT-PCR analizi, kontrol grubuyla karşılaştırıldığında, metimazol grubu sıçanlarda HB-EGF, EGFR, GPER1 ve ESR1 gen ekspresyonunun arttığını, RAF1 ekspresyonunun ise azaldığını ortaya koydu. Metimazol, sıçan yumurtalık foliküler gelişiminde ve oosit kalitesinde ciddi bozulmalara neden olur.
Ethical Statement
Bu araştırma, Pamukkale Üniversitesi Hayvan Deneyleri Etik Kurulu tarafından 'Deneysel Hipotiroidizmin Over Folikülleri Üzerine Etkisinin Değerlendirilmesi' başlığı ve PAUHADYEK-2023/08 numarası ile onaylanmıştır.
Supporting Institution
Bu araştırma Pamukkale Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi tarafından desteklenmiştir (Proje No: 2023SABE011).
Project Number
2023SABE011
Thanks
Katkılarından dolayı tüm yazarlara teşekkür ederiz
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-
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-
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EGFR expression in ovarian follicles of hypothyroid rats
Year 2026,
Volume: 43 Issue: 1
,
37
-
45
,
01.04.2026
Fatma Betül Silinmez
,
Hülya Çetin
,
İlknur Lafci
,
Semih Tan
,
Saim Özdamar
Abstract
Hypothyroidism causes a slowing of bodily functions as a result of insufficient production of thyroid hormones (T4 and T3). It also negatively affects reproductive health. Indeed, animal studies have shown that hypothyroidism inhibits follicular maturation and disrupts ovarian function. Epidermal growth factor (EGF) is a polypeptide that plays a vital role in cell growth and differentiation. This study aimed to investigate the effects of induced hypothyroidism in adult rats on ovarian follicles and changes in EGFR expression. Eighteen female Wistar rats were used in our study. Ten rats were randomly selected and given 10 mg/kg methimazole in their drinking water for 30 days, forming the hypothyroidism group. The remaining eight rats, which underwent no treatment, formed the control group. The effects of methimazole-induced experimental hypothyroidism on the ovary were investigated in terms of biochemical, histopathological, and mRNA expression changes. A significant decrease in serum T3 levels was observed in rats given methimazole. The mean body and ovary weights of rats in the hypothyroidism group, as well as the number of primary, secondary, and tertiary follicles, were found to be significantly reduced. Immunohistochemically, EGFR expression was also found to be reduced in rats in the hypothyroidism group. RT-PCR analysis revealed that, compared to the control group, the methimazole group rats had increased HB-EGF, EGFR, GPER1, and ESR1 gene expression, while RAF1 expression decreased. Methimazole causes severe impairments in rat ovarian follicular development and oocyte quality.
Ethical Statement
This research was approved by the Pamukkale University Animal Experiments Ethics Committee with the title 'Evaluation of The Effect of Experimental Hypothyroidism on Ovarian Follicles' and number PAUHADYEK-2023/08.
Supporting Institution
This research was supported by the Pamukkale University Scientific Research Projects Coordination Unit (Project No: 2023SABE011).
Project Number
2023SABE011
Thanks
We thank all authors for their contributions
References
-
Brown EDL, Obeng-Gyasi B, Hall JE, Shekhar S. The Thyroid Hormone Axis and Female Reproduction. Int J Mol Sci. 2023 Jun 6;24(12):9815. doi:10.3390/ijms24129815
-
Wu J, Zhao Y jie, Wang M, Tang M qiang, Liu Y fang. Correlation Analysis Between Ovarian Reserve and Thyroid Hormone Levels in Infertile Women of Reproductive Age. Front Endocrinol (Lausanne). 2021 Sep 27;12. doi:10.3389/fendo.2021.745199
-
Krassas GE, Poppe K, Glinoer D. Thyroid Function and Human Reproductive Health. Endocr Rev. 2010 Oct 1;31(5):702–55. doi:10.1210/er.2009-0041
-
Kabodmehri R, Sharami SH, Sorouri ZZ, Gashti NG, Milani F, Chaypaz Z, et al. The relationship between thyroid function and ovarian reserve: a prospective cross-sectional study. Thyroid Res. 2021 Dec 1;14(1):22. doi:10.1186/s13044-021-00112-2
-
Hapon MB, Gamarra-Luques C, Jahn GA. Short term hypothyroidism affects ovarian function in the cycling rat. Reproductive Biology and Endocrinology. 2010 Dec 11;8(1):14. doi:10.1186/1477-7827-8-14
-
Weng X, Ma X, Wang Q, Xu K, Hu X, Liu W, et al. Effect of hypothyroidism on CYP51 and FSHR expression in rat ovary. Theriogenology. 2019 Oct;138:145–51. doi:10.1016/j.theriogenology.2019.07.012
-
Rodríguez-Castelán J, Méndez-Tepepa M, Carrillo-Portillo Y, Anaya-Hernández A, Rodríguez-Antolín J, Zambrano E, et al. Hypothyroidism Reduces the Size of Ovarian Follicles and Promotes Hypertrophy of Periovarian Fat with
Infiltration of Macrophages in Adult Rabbits. Biomed Res Int. 2017;2017:1–11. doi:10.1155/2017/3795950
-
Palomba S, Colombo C, Busnelli A, Caserta D, Vitale G. Polycystic ovary syndrome and thyroid disorder: a comprehensive narrative review of the literature. Front Endocrinol (Lausanne). 2023 Aug 11;14. doi:10.3389/fendo.2023.1251866
-
Wang R, Lv Y, Dou T, Yang Q, Yu C, Guan Q. Autoimmune thyroid disease and ovarian hypofunction: a review of literature. J Ovarian Res. 2024 Jun 14;17(1):125. doi:10.1186/s13048-024-01451-y
-
Tuten A, Hatipoglu E, Oncul M, Imamoglu M, Acikgoz AS, Yilmaz N, et al. Evaluation of ovarian reserve in
Hashimoto’s thyroiditis. Gynecological Endocrinology. 2014 Oct 6;30(10):708–11. doi:10.3109/09513590.2014.926324
-
Batóg G, Dołoto A, Bąk E, Piątkowska-Chmiel I, Krawiec P, Pac-Kożuchowska E, et al. The interplay of oxidative stress and immune dysfunction in Hashimoto’s thyroiditis and polycystic ovary syndrome: a comprehensive
review. Front Immunol. 2023 Jul 31;14. doi:10.3389/fimmu.2023.1211231
-
Shih A, Zhang S, Cao HJ, Tang HY, Davis FB, Davis PJ, et al. Disparate Effects of Thyroid Hormone on Actions of Epidermal Growth Factor and Transforming Growth Factor-α Are Mediated by 3′,5′-Cyclic Adenosine 5′-
Monophosphate-Dependent Protein Kinase II. Endocrinology. 2004 Apr;145(4):1708–17. doi:10.1210/en.2003-0742
-
Jiang JY, Miyabayashi K, Nottola SA, Umezu M, Cecconi S, Sato E, et al. Thyroxine treatment stimulated ovarian follicular angiogenesis in immature hypothyroid rats. Histol Histopathol. 2008 Nov;23(11):1387–98. doi:10.14670/HH-23.1387 PubMed PMID: 18785121.
-
Meng L, Rijntjes E, Swarts H, Bunschoten A, van der Stelt I, Keijer J, et al. Dietary-Induced Chronic Hypothyroidism Negatively Affects Rat Follicular Development and Ovulation Rate and Is Associated with Oxidative Stress1. Biol Reprod. 2016 Apr 1;94(4). doi:10.1095/biolreprod.115.136515
-
Richani D, Gilchrist RB. The epidermal growth factor network: role in oocyte growth, maturation and developmental competence. Hum Reprod Update. 2018 Jan 1;24(1):1–14. doi:10.1093/humupd/dmx029
-
Franke TF, Yang SI, Chan TO, Datta K, Kazlauskas A, Morrison DK, et al. The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell. 1995 Jun;81(5):727–36. doi:10.1016/0092-8674(95)90534-0
-
Bjorge JD, Chan TO, Antczak M, Kung HJ, Fujita DJ. Activated type I phosphatidylinositol kinase is associated with the epidermal growth factor (EGF) receptor following EGF stimulation. Proceedings of the National Academy of Sciences. 1990 May;87(10):3816–20. doi:10.1073/pnas.87.10.3816
-
Yang YCSH, Ko PJ, Pan YS, Lin HY, Whang-Peng J, Davis PJ, et al. Role of thyroid hormone-integrin αvβ3-signal and
therapeutic strategies in colorectal cancers. J Biomed Sci. 2021 Apr 8;28(1):24. doi:10.1186/s12929-021-00719-5
Celep NA, Gedikli S, Parlak SN, Aliyev E. Experimental hypothyroidism increases oxidative stress and apoptosis in
ovary of rats. Original Article Eurasian Mol Biochem Sci [Internet]. 2023. Report. Available from: https://dergi.erzurum.edu.tr/ejmbs
-
Hayat NQ, Tahir M, Munir B, Sami W. Effect of methimazole-induced hypothyroidism on histological characteristics of parotid gland of albino rat. J Ayub Med Coll Abbottabad. 2010;22(3):22–7. PubMed PMID: 22338410.
-
Goldman JM, Murr AS, Cooper RL. The rodent estrous cycle: characterization of vaginal cytology and its utility in toxicological studies. Birth Defects Res B Dev Reprod Toxicol. 2007 Apr 6;80(2):84–97. doi:10.1002/bdrb.20106
-
Myers M, Britt KL, Wreford NGM, Ebling FJP, Kerr JB. Methods for quantifying follicular numbers within the mouse ovary. Reproduction. 2004 May;127(5):569–80. doi:10.1530/rep.1.00095
-
Silva JF, Ocarino NM, Serakides R. Thyroid hormones and female reproduction†. Biol Reprod. 2018 May 14. doi:10.1093/biolre/ioy115
-
König F, Andersson M, Hotz K, Aeberli I, Zimmermann MB. Ten Repeat Collections for Urinary Iodine from Spot Samples or 24-Hour Samples Are Needed to Reliably Estimate Individual Iodine Status in Women. J Nutr. 2011 Nov;141(11):2049–54. doi:10.3945/jn.111.144071
-
Meng L, Rijntjes E, Swarts HJM, Keijer J, Teerds KJ. Prolonged hypothyroidism severely reduces ovarian follicular reserve in adult rats. J Ovarian Res. 2017 Dec 16;10(1):19. doi:10.1186/s13048-017-0314-7
-
Rodrigues MS, Fallah HP, Zanardini M, Malafaia G, Habibi HR, Nóbrega RH. Interaction between thyroid hormones and gonadotropin inhibitory hormone in ex vivo culture of zebrafish testis: An approach to study multifactorial control of spermatogenesis. Mol Cell Endocrinol. 2021 Jul;532:111331. doi:10.1016/j.mce.2021.111331
-
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