Deneysel tirotoksikoz modelinde sıçan ovaryum dokusu rejenerasyon yeteneği ve kapasitesi

Amaç: Bu çalışmada, deneysel olarak tirotoksikoz oluşturulan sıçanlarda, tirotoksikoza bağlı olarak ovaryum yapısında, özellikle tiroid hormon reseptörleri içeren oosit, kumulus hücreleri ve gran ü losa hücrelerinde oluşabilecek histolojik değişimler ile doku rejenerasyon yeteneği ve kapasitesinin , kök hücre belirteçleri açısından imm ü nohistokimyasal olarak araştırılması amaçlan dı . Gereç ve Yöntem: Her biri 8 sıçandan oluşan 2 çalışma grubu oluşturul du. Tirotoksikoz grubu dişi sıçanlara 10 gün i ntraperitoneal 500µgr/kg/gün 3,3',5-Triiodo-L-thyronine enjekte edil di . On birinci gün tüm hayvanlara anestezi uygulan dı , biyokimyasal değerlendirmeler için 5 cc kan alındıktan sonra dekapite edilerek ovaryumları çıkarıl dı . Ovaryumlar immünohistokimyasal incelemeler için %4’ lük paraformaldehit fiksatifi içine alın dı . Rutin immünohistokimyasal takip ve boyamalar yapıl arak tüm örnekler ış ık mikroskobunda değerlendiril di . Bulgular: İmmünohistokimyasal boyamalar sonucunda c -kit ve Thy -1 ekspresyonu kontrol grubuna göre tirotoksikoz grubunda belirgin düzeyde azalmış, Nanog ekspresyonu ise tirotoksikoz grubunda artmış olarak bulundu. Tirotoksi kozlu sıçanlarda c -kit ve Thy -1’in azalması , tirotoksikozda stromal büyüme desteğinin azalmasına ve mikroçevre bozunumuna neden ol du. Sonuç: Tirotoksikozda Nanog ekspresyonunun artışı, foliküler yapıları ve oositleri korumak adına dokunun katabolik süreç (tiroid hormonlarının hemen tüm hücrelerde metabolizmayı hızlandırmasına bağlı olarak) artışına rağmen reaktif olarak mikroçevreyi koruma çabası olarak yorumlan dı .

Thyrotoxicosis in experimental rat model of ovarian tissue regeneration capability and capacity

Aim: In this study, it was aimed to investigate the possible histological changes in the ovarian structure and particularly in the oocytes, cumulus cells and granulosa cells containing thyroid hormone receptors, tissue regeneration capability and capacity in terms of stem cell markers immunohistochemically by experimentally-induced thyrotoxicosis in rats. Materials and Methods: Two study groups were formed (eight rats for each group); 500µgr/kg/day 3,3',5-Triiodo-L- thyronine was injected intraperitoneally to female rats in thyrotoxicosis group during ten days. In 11 th day, all animals were anesthesized, 5 cc blood was drawn for biochemical evaluation and then all were decapitated in order to remove ovaries. Ovaries were placed in 4% paraformaldehyde fixative for immunohistochemical investigation. Immunohystochemical processing and staining were performed routinely and all samples were evaluated by light microscopy.Results: As a result of immunohistochemical staining, c-kit and Thy-1 expressions were found to be significantly decreased in the thyrotoxicosis group compared with the control group, whereas Nanog expression was increased in the thyrotoxicosis group. Decrease in c-kit and Thy-1 expression in the thyrotoxicosis group cause d a reduction in the stimulatory effects of the growth factors on oocytes, cumulus and granulosa cells. Conclusion: Decreased levels of c-kit and Thy-1 in rat model of thyrotoxicosis lead to a decrease in stromal growth support and deterioration of microenvironment. Elevated levels of Nanog expression in thyrotoxicosis was interpreted as an effort to protect the microenvironment for the sake of follicles and oocytes despite the increase in catabolic processes (as a result of increased metabolism in almost all cells due to thyroid hormones).

___

  • 1. Zhang SS, Carrillo AJ, Darling DS. Expression of multiple thyroid hormone receptor mRNA in human oocytes, cumulus cells, and gran ulosa cells. Mol Hum Reprod 1997 ; 3 (7) :555 -62.
  • 2. Wang C, Crapo LM. The epidemiology of thyroid disease and implications for screening. Endocrinol Metab Clin North Am 1 997 ; 26(1):189 -218.
  • 3. Wakim AN, Polizotto SL, Buffo MJ, Marrero MA, Burholt DR. Thyroid hormones in human follicular fluid and thyroid hormone receptors in human gran u losa cells Fertil Steril 1993 ; 59 (6): 1187 -90 .
  • 4. Cecconi S, Rucci N, Scaldaferri ML , et al. Thyro id hormone effects on mouse oocyte maturation and gran u losa cell aromatase activity. Endocrinology 1999; 140 (4): 1783 -8.
  • 5. Krassas GE, Poppe K, Glinoer D. Thyroid function and human reproductive health. Endocr Rev 2010 ; 31 (5): 702 -55.
  • 6. Van Voorhis BJ, Neff TW, Sy rop CH, Chapler FK. Primary hypothyroidism associated with multicystic ovaries and ovarian torsion in adult. Obstet Gynecol 1994 ; 83 (5 Pt 2): 885 -7.
  • 7. Maruo T, Hayashi M, Matsuo H, Yamamoto T, Okada H, Mochizuki M. The role of thyroid hormone as biological amp lifier of the actions of follicle -stimulating hormone in the functional differentiation of cultured porcine gran u losa cell. Endocrinology 1987 ; 121 (4): 1233 -41.
  • 8. Dalçık H, Yıldırım M (Çeviri ed). Klinik Yönleriyle İnsan Embriyolojisi. 8. Baskı. İstanbul: Nobel Matbaacılık; 2009 : 173 -283 .
  • 9. Zamoner A, Barreto KP, Filho DW, et al. Hyperthyroidism in the developing rat testis is associated with oxidative stress and hyperphosphorylated vimentin accumulation. Mol Cell Endocrinol 2007;267 (1 -2):116 -26.
  • 10. O’Neal P, Alamdari N, Smith I, Poylin V, Menconi M, Hasselgren PO. Experimental h yperthyroidism in rats i ncreases the expression of the ubiquitin ligases a trogin -1 and MuRF1 and stimulates m ultiple p roteolytic pathways in s keletal m uscle. J Cell Biochem 2009;108 (4) :963 -73.
  • 11. Faraone -Mennella MR, Ferone A, Marino L, et al. Poly(ADP-ribosyl)ation of proteins and germ cell development in hyperthyroid rat testes. Mol Cell Biochem 2009;323 (1 -2):119 -29.
  • 12. Ismat F, Munawar A, Affi a T, et al. Antithyroid activity of some 6 -(alkylsulfanyl)-9 H-purines. J Serb Chem Soc 2011;76 (10)1355 - 64 .
  • 13. Ismat F, Munawar A, Affıa T, Asmatullah A, Khan MA. Assessment of antithyroid activity of 2,8 -disulfanyl -1, 9 -dihydro -6H-purin - 6 -one in vitro and in vivo. Med Chem Res 2011; DOI 10.1007/s00044 -011 -9608 -2 (published online) .
  • 14. Erdoğan G. Koloğlu Endokrinoloji - Temel ve Klinik. 2.Baskı . Adana: Nobel Yayınevi; 2005 : 155 -280 .
  • 15. Tunbridge WM, Evered DC, Hall R , et al. The spectrum of thyroid disease in a community: The Whickham survey. Clin Endocrinol 1977 ; 7(6):481 -93.
  • 16. Cramer DW, Sluss PM, Powers RD, et al. Serum p rolactin and TSH in an i n -vitro fertilization p opulation: Is there a l ink b etween f ertilization and thyroid function? J Assist Reprod Genet 2003 ; 20 (6):210 -5.
  • 17. Longcope C. The male and female reproductive sys tem in hypothyroidism. In: Ingbar SH, Bravermann LE (eds) . The Thyroid. Philadelphia: Lippincott; 1991 : 1052 -5.
  • 18. Cle´ment K, Viguerie N, Diehn M , et al. In vivo regulation of human skeletal muscle gene expression by thyroid hormone. Genome Res 2002 ; 12 (2) :281 -91 .
  • 19. Krassas GE, Poppe K, Glinoer D. Thyroid function and human reproductive health. Endocr Rev 2010, 31 (5);702 -55.
  • 20. Zhang SS, Carrillo AJ, Darling DS. Expression of multiple thyroid hormone receptor mRNAs in human oocytes, cumulus cells, and gran ulosa cell s, Mol Human Reprod 1997 ; 3(7): 555 -62.
  • 21. Goldman S, Dirnfeld M, Gonen Y, Koifman M, Lissak A, Abramovici H . Different morphology and proliferative ability of cumulus and gran ulosa cells originating from cystic follicles aspirated from stimulated in vitro fertilization patients. Fertil Steril 1993 ; 59 (3): 601 -5.
  • 22. Rae MT, Niven D, Ross A, et al. Steroid signalling in human ovarian surface epithelial cells: The response to interleukin -1 determined by microarray analysis. J Endocrinol 2 004; 183 (1) :19 -28 .
  • 23. Horie K, Fuji ta J, Takakura K, et al. The expression of c -kit protein in human adult and fetal tissues. Hum Reprod 1993 ; 8 (11) ;1955 -62.
  • 24. Gougeon A , Busso D. Morphologic and functional determinants of primordial and primary follicles in the mo nkey ovary. Mol Cell Endocrin ol 2000 ; 163 (1 -2): 33 -42.
  • 25. Clark DE, Tisdall DJ, Fidler AE, McNatty KP. Localization of mRNA encoding c -kit during the initiation of folliculogenesis in ovine fetal ovaries. J Reprod Fertil 1996 ; 106 (2): 329 -35.
  • 26. Motro B, Bernstein A. Dynamic changes in ovarian c -kit and s teel expression during the estrous reproductive cycle. Dev Dyn 1993 ; 197 (1): 69 -79.
  • 27. Doneda L, Klinger FG, Larizza L and De Felici M. KL/KIT co -expression in mouse fetal oocytes. Int J Dev Biol 2002 ; 46 (8): 1015 - 21.
  • 28. Hutt KJ, Mc Laughlin EA, Holland M K. Kit ligand and c-Kit have diverse roles during mammalian oogenesis and folliculogenesis. Mol Hum Reprod 2006 ; 12 (2): 61 -9.
  • 29. Manova K, Huang EJ, Angeles M. The expression pattern of the c-kit ligand in gonads of mice supports a role for the c-kit receptor i n oocyte growth and in proliferation of spermatogonia. Dev Biol 1993 ; 157 (1): 85-99.
  • 30. Manova K, Bachvarova RF. Expression of c-kit encoded at the W locus of mice in developing embryonic germ cells and presumptive melanoblasts. Dev Biol 1991 ; 146 (2): 312 -24.
  • 31. Kan g JS, Lee CJ, Lee JM, Rha JY, Song KW, Park MH. Follicular expression of c -Kit/SCF and inhibin -alpha in mouse ovary during development. J Histochem Cytochem 2003 ; 51 (11): 1447 -58.
  • 32. Robinson LL, Gaskell TL, Saunders PTK, Anderson RA. Germ cell specific express ion of c-kit in the hu man fetal gonad. Mol Hum Reprod 2001 ; 7 (9): 845 -52.
  • 33. Hoyer PE, Byskov AG, Mollgard K. Stem cell factor and c -k it in human primordial germ cells and fetal o varies. Mol Cell Endocrinol 2005 ; 234 (1 -2): 1 -10.
  • 34. Abir R, Fisch B, Jin S, Barnnet M, Kessler-Icekson G, Ao A. Expression of stem cell factor and its receptor in human fetal and adult ovaries. Fertil Steril 2004 ;8(Suppl 3): 1235 -43.
  • 35. Rege TA, Hagood JS. Thy -1, a versatile modulator of signaling affecting cellular adhesion, proliferation, survival, and cytokine/growth factor responses . Biochim Biophys Acta 2006 ; 1763(10):991 -9.
  • 36. Xue GP, Calvert RA, Morris RJ. Expression of the neuronal surface glycoprotein Thy -1 is under posttranscriptional control, and is spatially regulated, in the developing olfactory system. Development 1990 ; 109 (4):851 -64.
  • 37. Bukovsky A, Caudle MR, Svetlikova M, Upadhyaya NB. Origin of germ cells and formation of new primary follicles in adult human ovaries. Reprod Biol Endocrinol 2004 ;28(2):20 -2.
  • 38. Bukovsky A, Caudle MR, Keenan J A, Wimalasena J, Foster JS, Van Meter SE. Quantitative evaluation of the cell cycle -related retinoblastoma protein and localization of Thy -1 differentiation protein and macrophages during follicular development and atresia, and in human corpora lutea. Biol Reprod 1995 ; 52 (4): 776-92.
  • 39. Bukovsky A, Caudle MR, Svetlikova M, Wimalasena J, Ayala ME, Dominguez R. Oogenesis in a dult mammals , i ncluding humans . Endocrine 2005 ; 26 (3 ): 301 -6.
  • 40. Kerr CL, Hill CM, Blumenthal PD, Gearhart JD. Expression of pluripotent stem cell markers in the human fetal ovary. Hum Reprod 2008 ; 23 (3 ): 589 -99.
  • 41. Hoei -Hansen CE, Kraggerud SM, Abeler VM, Kaern J, Rajpert-De Meyts E, Lothe RA. Ovarian dysgerminomas are characterised by frequent KIT mutations and abundant expression of pluripotency marke rs. Mol Cancer 2007 ;2(6 ):12 -4 .
  • 42. Stoop H, Honecker F, Cools M, de Krijger R, Bokemeyer C, Looijenga LH. Differentiation and development of human female germ cells during prenatal gonadogenesis: An immunohistochemical study. Hum Reprod 2005 ; 20 (6) :1466 -76.
Ege Tıp Dergisi-Cover
  • ISSN: 1016-9113
  • Yayın Aralığı: Yılda 4 Sayı
  • Başlangıç: 1962
  • Yayıncı: Ersin HACIOĞLU
Sayıdaki Diğer Makaleler

AML ön tanılı olgularda inv(16) CBFBETA- MYH11 inversiyonunun real time RT - PCR ile 5 yıllık sonuçlarının değerlendirilmesi

ASLI TETİK VARDARLI, SUNDE YILMAZ SÜSLÜER, .Çağdaş AKTAN, Çağla KAYABAŞI, Çığır AVCI BİRAY, Serap AKSOYLAR, Deniz YILMAZ, Mahmut TÖBÜ, Fahri ŞAHİN, Burçin KAYMAZ TEZCANLI, DUYGU DÖNDÜ AYGÜNEŞ JAFARI, Ali Şahin KÜÇÜKASLAN, Besra YELKEN ÖZMEN, BUKET KOSOVA, Nazan ÇETİNGÜL, Yeşim AYDINOK, MURAT TOMBULOĞLU, Güray SAYDAM

Enterokutan fistülün nadir bir sebebi: İntraperitoneal mesh katlantısı

Ömer ENGİN, Mehmet YILMAZ, Ulaş URGANCI

Oftalmik cerrahide anestezi

Canan BOR, Agah ÇERTUĞ

Histeroskopik polipektomi esnasında uterin rüptür

İsmet HORTU, Burak ZEYBEK, Ahmet Mete ERGENOĞLU, Ali AKDEMİR, Ahmet Özgür YENİEL

Deneysel tirotoksikoz modelinde sıçan ovaryum dokusu rejenerasyon yeteneği ve kapasitesi

Fatih OLTULU, Hüseyin AKTUĞ, AYŞEGÜL UYSAL, Gülperi ÖKTEM, Nevbahar TURGAN, Nefise Ülkü YAVAŞOĞLU KARABAY, ALTUĞ YAVAŞOĞLU

Proksimal üreter taşı olan 96 olguda ESWL tedavisi sonuçları

Tufan SÜELÖZGEN, HAKAN TÜRK, Cemal Selçuk İŞOĞLU, Mehmet YOLDAŞ, Mustafa KARABIÇAK, Batuhan ERGANİ, Yusuf Özlem İLBEY, Ferruh ZORLU

Bilateral ovarian capillary hemangioma

İbrahim GELİNCİK, ILYAS SAYAR, Ali KURT, Ali YİTİK

Son dönem böbrek yetmezliğinin nadir bir nedeni: Fabry hastalığı

Bennur ESEN, Ahmet Engin ATAY, Emel GÖKMEN, Süleyman YILDIRIM, DEDE ŞİT

Sağlıklı gözlerde optik koherens tomografi ile maküler kalınlık ölçümü: Yaş ve cinsiyete bağlı değişimler

İHSAN YILMAZ, Çağrı MUTAF, Turgay SATICI, Ferah ÖZÇELİK, Ahmet Taylan YAZICI, Ahmet DEMİROK

Kombine preparat ya da tek başına uzun etkili beta agonist kullanan kronik obstrüktif akciğer hastalığı olgularında pnömoni gelişme oranının retrospektif olarak karşılaştırılması

Tuğba ÖNALAN, Ayşegül BAYSAK, Jülide EMRE ÇELDİR, Özer ÖZDEMİR, Mustafa Hikmet ÖZHAN