Experimental hypothyroidism increases oxidative stress and apoptosis in ovary of rats

Yıl 2023, Cilt: 2 Sayı: 2, 21 - 29, 25.10.2023

Nevra Aydemir Celep , Semin Gedikli , Seçil Nazife Parlak , Elvin Aliyev

Öz

This study aimed to investigate Hypothyroidism's effects in experimental hypothyroidism-induced female rats. Materials and Methods: To induce Hypothyroidism in rats, 0.05% 6-propyl-2-thiouracil (PTU) was given orally to the Hypothyroid (HT) and L-thyroxine (LT) groups with their drinking water for eight weeks. In the LT group, 0.8 µg/100 g L-thyroxine was provided by subcutaneous for ten days of the experiment. Results: In the histopathological evaluation, Hypothyroidism induced severe dilation in vessels atretic and irregular follicles and damaged the germinal epithelium. These pathologies were decreased in the LT group. In the biochemical analysis, SOD activity, GSH activity, and MDA level were lower in the HT group than Control and LT groups. In the relative protein analysis, Caspase-3, mTOR, P2X7R, NfkB, IL-1β, and TNF-α levels were lower in the Control and LT groups, but the relative protein expression of Caspase-3, mTOR, P2X7R, NfkB, IL-1β, and TNF-α was found as higher in the HT group. The protein expression of Bcl-2 level was higher in the Control and LT groups. Conclusion: The results showed that Hypothyroidism causes ovary tissue injuries —the histopathological and biochemical changes induced by Hypothyroidism in the experimental rat model were ameliorated with L-thyroxine treatment.

Anahtar Kelimeler

Hypothyroidism, ovary, oxidative stress, rat

Kaynakça

• 1. Pearce EN. Thyroid dysfunction in perimenopausal and postmenopausal women. Menopause international 2007;13:8-13.
• 2. Vanderpas J. Nutritional epidemiology and thyroid hormone metabolism. Annu Rev Nutr 2006;26:293-322.
• 3. Ozkanlar S, Kara H, Gür C, Gedikli S, Kara A, Ozudogru Z, et al. Effects of photoperiod on thyroid gland development and function in growing chicks: a biochemical and morphometric study. Animal Production Science 2021;61:1652-8.
• 4. Vissenberg R, Manders V, Mastenbroek S, Fliers E, Afink G, Ris-Stalpers C, et al. Pathophysiological aspects of thyroid hormone disorders/thyroid peroxidase autoantibodies and reproduction. Human reproduction update 2015;21:378-87.
• 5. Abalovich M, Mitelberg L, Allami C, Gutierrez S, Alcaraz G, Otero P, et al. Subclinical hypothyroidism and thyroid autoimmunity in women with infertility. Gynecological Endocrinology 2007;23:279-83.
• 6. Joshi J, Bhandarkar S, Chadha M, Balaiah D, Shah R. Menstrual irregularities and lactation failure may precede thyroid dysfunction or goitre. Journal of postgraduate medicine 1993;39:137.
• 7. Krassas G, Pontikides N, Kaltsas T, Papadopoulou P, Paunkovic J, Paunkovic N, et al. Disturbances of menstruation in hypothyroidism. Clinical endocrinology 1999;50:655-9.
• 8. DORRINGTON J, CHUMA AV, BENDELL JJ. Transforming growth factor β and follicle-stimulating hormone promote rat granulosa cell proliferation. Endocrinology 1988;123:353-9.
• 9. Teerds KJ, Dorrington JH. Immunohistochemical localization of transforming growth factor-β1 and-β2 during follicular development in the adult rat ovary. Molecular and cellular endocrinology 1992;84:R7-R13.
• 10. Danilovich N, Wernsing D, Coschigano K, Kopchick J, Bartke A. Deficits in female reproductive function in GH-R-KO mice; role of IGF-I. Endocrinology 1999;140:2637-40.
• 11. Almog B, Gold R, Tajima K, Dantes A, Salim K, Rubinstein M, et al. Leptin attenuates follicular apoptosis and accelerates the onset of puberty in immature rats. Molecular and Cellular Endocrinology 2001;183:179-91.
• 12. Lagaly DV, Aad PY, Grado-Ahuir JA, Hulsey LB, Spicer LJ. Role of adiponectin in regulating ovarian theca and granulosa cell function. Molecular and Cellular Endocrinology 2008;284:38-45.
• 13. Kobayashi N, Orisaka M, Cao M, Kotsuji F, Leader A, Sakuragi N, et al. Growth differentiation factor-9 mediates follicle-stimulating hormone-thyroid hormone interaction in the regulation of rat preantral follicular development. Endocrinology 2009;150:5566-74.
• 14. Zhang C, Guo L, Zhu B, Feng Y, Yu S, An N, et al. Effects of 3, 5, 3′-triiodothyronine (t3) and follicle stimulating hormone on apoptosis and proliferation of rat ovarian granulosa cells. Chin J Physiol 2013;56:298-305.
• 15. Erbaş E, Gedikli S. Investigation of the endometrial receptivity status in experimental hypothyroid-induced female rats. Iranian Journal of Basic Medical Sciences 2022;25.
• 16. Devdhar M, Ousman Y, Burman K. Hypothyroidism Endocrinol Metab Clin North Am, 36 (2007). View PDF View article View in Scopus:595-615.
• 17. Krassas G, Poppe K, Glinoer D. Thyroid function and human reproductive health. Endocrine reviews 2010;31:702-55.
• 18. Soliman FA, Reineke E. Influence of variations in environmental temperature and thyroid status on sexual function in young female mice. American Journal of Physiology-Legacy Content 1952;168:400-5.
• 19. Rivkees SA, Mattison DR. Propylthiouracil (PTU) hepatoxicity in children and recommendations for discontinuation of use. International journal of pediatric endocrinology 2009;2009:1-8.
• 20. Dijkstra G, de Rooij DG, de Jong FH, van den Hurk R. Effect of hypothyroidism on ovarian follicular development, granulosa cell proliferation and peripheral hormone levels in the prepubertal rat. European Journal of Endocrinology 1996;134:649-54.
• 21. Fedail JS, Zheng K, Wei Q, Kong L, Shi F. Roles of thyroid hormones in follicular development in the ovary of neonatal and immature rats. Endocrine 2014;46:594-604.
• 22. Dobrzyńska MM, Baumgartner A, Anderson D. Antioxidants modulate thyroid hormone‐and noradrenaline‐induced DNA damage in human sperm. Mutagenesis 2004;19:325-30.
• 23. Polat S, Topal H, Celep NA, Erbaş E, Adem K. Melatonin and cisplatin synergistically enhance apoptosis via autophagy-dependent alteration of P53 transcription in human colorectal cancer cells. Eurasian Journal of Molecular and Biochemical Sciences 2022;1:11-8.
• 24. Zuo L, Zhou T, Pannell B, Ziegler A, Best TM. Biological and physiological role of reactive oxygen species–the good, the bad and the ugly. Acta physiologica 2015;214:329-48.
• 25. Behrman HR, Kodaman PH, Preston SL, Gao S. Oxidative stress and the ovary. Journal of the Society for Gynecologic Investigation 2001;8:S40-S2.
• 26. Takami M, Preston S, Toyloy V, Behrman HR. Antioxidants reversibly inhibit the spontaneous resumption of meiosis. American Journal of Physiology-Endocrinology and Metabolism 1999;276:E684-E8.
• 27. Ruder EH, Hartman TJ, Blumberg J, Goldman MB. Oxidative stress and antioxidants: exposure and impact on female fertility. Human reproduction update 2008;14:345-57.
• 28. Armada-Dias L, Carvalho J, Breitenbach M, Franci CR, Moura EG. Is the infertility in hypothyroidism mainly due to ovarian or pituitary functional changes? Brazilian Journal of Medical and Biological Research 2001;34:1209-15.
• 29. Moulakakis KG, Poulakou MV, Dosios T, Dontas I, Sokolis DP, Vlachos IS, et al. Hypothyroidism and the aorta. evidence of increased oxidative DNA damage to the aorta of hypothyroid rats. in vivo 2008;22:603-8.
• 30. Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clinical chemistry 1988;34:497-500.
• 31. Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Analytical biochemistry 1968;25:192-205.
• 32. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical biochemistry 1979;95:351-8.
• 33. Dalton AJ, Morris HP, Dubnik CS. Changes in the organs of female C3H mice receiving thiourea. JNCI: Journal of the National Cancer Institute 1945;5:451-4.
• 34. You HH, Song G. Review of endocrine disruptors on male and female reproductive systems. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 2021;244:109002.
• 35. Jiang J, Umezu M, Sato E. Improvement of follicular development rather than gonadotrophin secretion by thyroxine treatment in infertile immature hypothyroid rdw rats. Journal of reproduction and fertility 2000;119:193-200.
• 36. Meng L, Rijntjes E, Swarts HJ, Keijer J, Teerds KJ. Prolonged hypothyroidism severely reduces ovarian follicular reserve in adult rats. Journal of ovarian research 2017;10:1-8.
• 37. Gedikli S, Gelen V, Sengul E, Ozkanlar S, Gur C, Agırbas O, et al. Therapeutic effects of melatonin on liver and kidney damages in intensive exercise model of rats. Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets-Immune, Endocrine & Metabolic Disorders) 2015;15:308-14.
• 38. 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 stress. Biology of reproduction 2016;94:90, 1-11.
• 39. Dardano A, Ghiadoni L, Plantinga Y, Caraccio N, Bemi A, Duranti E, et al. Recombinant human thyrotropin reduces endothelium-dependent vasodilation in patients monitored for differentiated thyroid carcinoma. The Journal of Clinical Endocrinology & Metabolism 2006;91:4175-8.
• 40. Haribabu A, Reddy VS, Pallavi C, Bitla AR, Sachan A, Pullaiah P, et al. Evaluation of protein oxidation and its association with lipid peroxidation and thyrotropin levels in overt and subclinical hypothyroidism. Endocrine 2013;44:152-7.
• 41. Coria MJ, Pastrán AI, Gimenez MS. Serum oxidative stress parameters of women with hypothyroidism. 2009.
• 42. Erdamar H, Demirci H, Yaman H, Erbil MK, Yakar T, Sancak B, et al. The effect of hypothyroidism, hyperthyroidism, and their treatment on parameters of oxidative stress and antioxidant status. Clinical chemistry and laboratory medicine 2008;46:1004-10.
• 43. He J, Zhou Y, Zhang T, Zou Y, Huang H. Effect of Bushen Antai recipe on pyroptosis mechanism of subclinical hypothyroidism decidual cells in early pregnancy. Annals of Translational Medicine 2022;10.
• 44. Vishwakarma J, Gupta K, Mishra J, Garg A, Malik R, Kashyap A, et al. Hypothyroidism induces motor deficit via altered cerebellar HB-EGF/EGFR and autophagy. The Journal of endocrinology 2023;257:e220338.