Abstract
Amaç: ADAM TS proteinleri, transmembran glikoproteinlerdir.ADAMTS ailesindeki proteazlarda disregülasyon veya fonksiyonel değişiklikler, polikistik over sendromu (PCOS) ve prematür over yetmezliği (POF) gibi üreme bozukluklarıyla ilişkilendirilmiştir. Bu çalışmada; follikül epitelinde ADAMTS 16 ekspresyonunun FSH ve LH ile ilişkisinin irdelenmesi amaçlanmıştır.
Gereç ve Yöntem: Çalışmaya 2013-2015 yılları arasında ooferektomi geçirmiş olan ve alınan doku örnekleri patoloji bölümüne gönderilen, yaş aralığı 18-55 yıl olan toplam 78 vaka dahil edildi. Vakalara ait parafin bloklardan polilizinli lam üzerine, 3 mikrometre kalınlığında kesitler alındı. Bu kesitlere ABC tekniği ile imuunohistokimyasal olarak FSH, LH ve ADAMTS-16 uygulandı. Işık mikroskobu altında boyanma değerlenrilirken; yok:0,hafif boyanma:1, orta:2, şiddetli:3 olarak derecelendirildi. Çalışmada hastalardan alınan örnekler üzerinde yapılan patolojik inceleme sonrasında yapılan LH, FSH, ADAM TS -16 boyanma sonuçlarının (Yok, Var) birbirleriyle ve hastaların yaşı ile arasındaki bağımlılık yapısını incelemek amacı ile ki-kare analizi kullanılmıştır. Tüm istatistiksel hesaplamalar SPSS 19.0 V istatistik paket programında yapılmış olup bulgular n ve yüzde olarak ifade edilmiştir.
Bulgular: Hastalardan alınan örnekler üzerinde yapılan patolojik inceleme sonrasında yapılan LH, FSH ve ADAMTS -16 boyanma sonuçlarının hastaların yaşına göre değişmediği belirlenmiştir (sırasıyla; P=0.215, P=0.665 ve P=0.508).Hastalardan alınan örnekler üzerinde yapılan patolojik inceleme sonrasında yapılan LH boyanma sonuçlarının FSH boyanma sonuçlarına bağlı olarak değiştiği (P<0,001) ve LH boyanma sonuçlarının da ADAMTS -16 boyanma sonuçlarına göre değiştiği (P<0.05) belirlenmiştir. FSH boyanma sonuçlarının ise ADAMTS -16 boyanma sonuçlarına göre değişmediği belirlenmiştir (P=0,308).
Sonuç: ADAMTS’lerin rollerine yeni bir bakış açısı; doğurganlığın ardındaki moleküler mekanizmaları daha derinlemesine anlamayı ve üreme organlarının işlev bozukluğunu öngören biyolojik belirteçlerin geliştirilmesini sağlayacaktır.
Anahtar Kelimeler: Ooferektomi, ADAMTS-16, FSH, LH.
Abstract
Objective: ADAM TS proteins are transmembrane glycoproteins. Dysregulation or functional changes in the proteases in the ADAM TS family are related to reproductive disorders like polycystic ovarian syndrome (PCOS) and premature ovarian failure (POF).
In this study, an attempt was made to determine the correlation between ADAM TS-16 expression with FSH and LH in follicular epithelium.
Materials and Methods: A total of 78 cases, whose age range was 18-55 years, who had undergone oophorectomy between 2013-2015 and whose tissue samples were sent to the
pathology department, were included in the study. From the paraffin blocks belonging to the cases, 3 micrometer thick sections were taken on the polilizin slide. FSH, LH and ADAMTS-16 were applied imuunohistochemically to these sections with ABC technique. While the staining is evaluated under light microscope; None: 0, mild staining: 1, medium: 2, severe: 3.
In the study, chi-square analysis was used to examine the dependence structure of LH, FSH, ADAM TS -16 staining results (None, Var) between each other and the age of the patients after the pathological examination on the samples taken from the patients. All statistical calculations are made in SPSS 19.0 V statistical package program and the findings are expressed as n and percent.
Results: LH, FSH and ADAMTS -16 staining results after the pathological examination on the samples taken from the patients did not change according to the age of the patients (P = 0.215, P = 0.665 and P = 0.508, respectively).
It was determined that the results of LH staining performed after the pathological examination on the samples taken from the patients changed depending on the FSH staining results (P <0.001) and the results of the LH staining changed according to the ADAMTS -16 staining results (P<0.05). FSH staining results did not change according to ADAMTS -16 staining results (P|> 0.05).
Conclusion: A new perspective on the roles of ADAMTS; It will provide a deeper understanding of the molecular mechanisms behind fertility and the development of biological markers that predict dysfunction of the reproductive organs.
Keywords
Supporting Institution
Ordu Üniversitesi BAP birimi
Project Number
AR-1510
Thanks
Çalışmamızın istatistik analizlerinde yardım ve danışmanlığını esirgemeyen Prof. Dr. Soner ÇANKAYA'ya desteği için çok teşekkür ederiz.
References
- KAYNAKLAR 1. Fatma Bahar Sunay, Sümeyye Aydogan Türkoğlu, Feray Köçkar. ADAMTS Ailesi ve Anti-Anjiogenetik ADAMTS1. Uludağ Üniversitesi Tıp Fakültesi Dergisi 38 (1) 49-56, 2012. 2. Porter S., Clark I.M., Kevorkian L., Edwards D.R. The ADAMTS metalloproteinases. Biochem. J.2005;386: 15–27. 3. Cal S., Obaya A.J., Llamazares M., Garabaya C., Quesada V., Lopez-Otin C. Cloning, expression analysis, and structural characterization of seven novel human ADAMTSs, a family of metalloproteinases with disintegrin and thrombospondin-1 domains. Gene. 2002;283:49–62. 4. Huxley-Jones J., Apte S.S., Robertson D.L., Boot-Handford R.P. The characterisation of six ADAMTS proteases in the basal chordate Ciona intestinalis provides new insights into the vertebrate ADAMTS family.Int. J. Biochem. Cell Biol. 2005;37:1838–1845. 5. Tortorella MD, Malfait F, Barve RA, Shieh HS, Malfait AM. A review of the ADAM TS family, pharmaceutical targets of the future. (Curr Pharm Des. 2009;15(20):2359-74.). 6. Rodgers U.R., Kevorkian L., Surridge A.K., Waters J.G., Swingler T.E., Culley K., Illman S., Lohi J., Parker A.E., Clark I.M. Expression and function of matrix metalloproteinase (MMP)-28. Matrix Biol.2009;28:263–272. 7. Cal S., Obaya A.J., Llamazares M., Garabaya C., Quesada V., Lopez-Otin C. Cloning, expression analysis, and structural characterization of seven novel human ADAMTSs, a family of metalloproteinases with disintegrin and thrombospondin-1 domains. Gene. 2002;283:49–62. 8. Hirohata S., Wang L.W., Miyagi M., Yan L., Seldin M.F., Keene D.R., Crabb J.W., Apte S.S., "Punctin, a novel ADAMTS-like molecule, ADAMTSL-1, in extracellular matrix", The Journal of Biological Chemistry, (2002), 277, 14, 12182. 9. Tang B.L., "ADAMTS: a novel family of extracellular matrix proteases", The International Journal of Biochemistry and Cell Biology, (2001), 33, 33. 10. Russell DL, Brown HM, Dunning KR. ADAMTS proteases in fertility. Matrix Biol. 2015 Mar 26. pii: S0945-053X(15)00058-X. doi: 10.1016/j.matbio.2015.03.007. 11. Gao S., De Geyter C., Kossowska K., Zhang H. FSH stimulates the expression of the ADAMTS-16 protease in mature human ovarian follicles. Mol. Hum. Reprod. 13:465–471, 2007. 12. Espey LL, Yoshioka S, Russell DL, Robker RL, Fujii S, Richards JS, et al. Ovarian expression of a disintegrin and metalloproteinase with thrombospondin motifs during ovulation in the gonadotropin-primed immature rat. Biol Reprod 2000;62:1090–5. 13. Wolfsberg TG, Primakoff P, Myles DG, White JM. ADAM, a novel family of membrane proteins containing A Disintegrin And Metalloprotease domain: multipotential functions in cell-cell and cell-matrix interactions. J Cell Biol. 1995;131:275-8. 14. Pyun JA, Kim S, Cha DH, Kwack K. Epistasis between IGF2R and ADAMTS19 polymorphisms associates with premature ovarian failure. Human Rep. 2013;28:3146-54. 15. Espey LL, Yoshioka S, Russell DL, Robker RL, Fuji S, Richards JS. Ovarian expression of a disintegrin and metalloproteinase with thrombospondin motifs during ovulation in the gonadotropin-primed immature rat. Biol Reprod 2000;62:1090–1095. 16. Richards JS, Hernandez-Gonzalez I, Gonzalez-Robayna I, Teuling E, Lo Y, Boerboom D, Falender AE, Doyle KH, LeBaron RG, Thompson V et al. Regulated expression of ADAMTS family members in follicles and cumulus oocyte complexes: evidence for specific and redundant patterns during ovulation. Biol Reprod 2005;72:1241–1255) 17. Kikuno R, Nagase T, Nakayama M, Koga H, Okazaki N, Nakajima D, Ohara O. HUGE: a database for human KIAA proteins, a 2004 update integrating HUGEppi and ROUGE. Nucleic Acids Res 2004;32:D502–D504) 18. Freimann S, Ben-Ami I, Dantes A, Armon L, Ben Ya'cov-Klein A, Ron-El R, et al. Differential expression of genes coding for EGF-like factors and ADAMTS1 following gonadotropin stimulation in normal and transformed human granulosa cells. Biochem Biophys Res Commun 2005;333:935–43. 19. Russell DL, Doyle KMH, Ochsner SA, Sandy JD, Richards JS. Processing and localization of ADAMTS-1 and proteolytic cleavage of versican during cumulus matrix expansion and ovulation. J Biol Chem 2003b;278: 42330–42339. 20. Ress D.G., 1987. Foundations of Statistics, Chapman and Hall, NewYork. 21. Doyle KM, Russell DL, Sriraman V, Richards JS. Coordinate transcription of the ADAMTS-1 gene by luteinizing hormone and progesterone receptor. Mol Endocrinol 2004;18:2463–78.) 22. Shindo T, Kurihara H, Kuno K, Yokoyama H, Wada T, Kurihara Y, et al. ADAMTS-1: a metalloproteinase-disintegrin essential for nor¬mal growth, fertility, and organ morphology and function. J Clin Invest 2000;105:1345-52. 23. Jung-A Pyun, Sunshin Kim, KyuBum Kwack. Interaction between thyroglobulin and ADAMTS16 in premature ovarian failure. Clin Exp Reprod Med 2014;41(3):120-124 24. Willis EL, Bridges PJ, Fortune JE. Progesterone receptor and prostaglandins mediate luteinizing hormone-induced changes in messenger RNAs for ADAMTS proteases in theca cells of bovine periovulatory follicles. Mol Reprod Dev. 2016 Nov 23. doi: 10.1002/mrd.22761.
Abstract
Project Number
AR-1510
References
- KAYNAKLAR 1. Fatma Bahar Sunay, Sümeyye Aydogan Türkoğlu, Feray Köçkar. ADAMTS Ailesi ve Anti-Anjiogenetik ADAMTS1. Uludağ Üniversitesi Tıp Fakültesi Dergisi 38 (1) 49-56, 2012. 2. Porter S., Clark I.M., Kevorkian L., Edwards D.R. The ADAMTS metalloproteinases. Biochem. J.2005;386: 15–27. 3. Cal S., Obaya A.J., Llamazares M., Garabaya C., Quesada V., Lopez-Otin C. Cloning, expression analysis, and structural characterization of seven novel human ADAMTSs, a family of metalloproteinases with disintegrin and thrombospondin-1 domains. Gene. 2002;283:49–62. 4. Huxley-Jones J., Apte S.S., Robertson D.L., Boot-Handford R.P. The characterisation of six ADAMTS proteases in the basal chordate Ciona intestinalis provides new insights into the vertebrate ADAMTS family.Int. J. Biochem. Cell Biol. 2005;37:1838–1845. 5. Tortorella MD, Malfait F, Barve RA, Shieh HS, Malfait AM. A review of the ADAM TS family, pharmaceutical targets of the future. (Curr Pharm Des. 2009;15(20):2359-74.). 6. Rodgers U.R., Kevorkian L., Surridge A.K., Waters J.G., Swingler T.E., Culley K., Illman S., Lohi J., Parker A.E., Clark I.M. Expression and function of matrix metalloproteinase (MMP)-28. Matrix Biol.2009;28:263–272. 7. Cal S., Obaya A.J., Llamazares M., Garabaya C., Quesada V., Lopez-Otin C. Cloning, expression analysis, and structural characterization of seven novel human ADAMTSs, a family of metalloproteinases with disintegrin and thrombospondin-1 domains. Gene. 2002;283:49–62. 8. Hirohata S., Wang L.W., Miyagi M., Yan L., Seldin M.F., Keene D.R., Crabb J.W., Apte S.S., "Punctin, a novel ADAMTS-like molecule, ADAMTSL-1, in extracellular matrix", The Journal of Biological Chemistry, (2002), 277, 14, 12182. 9. Tang B.L., "ADAMTS: a novel family of extracellular matrix proteases", The International Journal of Biochemistry and Cell Biology, (2001), 33, 33. 10. Russell DL, Brown HM, Dunning KR. ADAMTS proteases in fertility. Matrix Biol. 2015 Mar 26. pii: S0945-053X(15)00058-X. doi: 10.1016/j.matbio.2015.03.007. 11. Gao S., De Geyter C., Kossowska K., Zhang H. FSH stimulates the expression of the ADAMTS-16 protease in mature human ovarian follicles. Mol. Hum. Reprod. 13:465–471, 2007. 12. Espey LL, Yoshioka S, Russell DL, Robker RL, Fujii S, Richards JS, et al. Ovarian expression of a disintegrin and metalloproteinase with thrombospondin motifs during ovulation in the gonadotropin-primed immature rat. Biol Reprod 2000;62:1090–5. 13. Wolfsberg TG, Primakoff P, Myles DG, White JM. ADAM, a novel family of membrane proteins containing A Disintegrin And Metalloprotease domain: multipotential functions in cell-cell and cell-matrix interactions. J Cell Biol. 1995;131:275-8. 14. Pyun JA, Kim S, Cha DH, Kwack K. Epistasis between IGF2R and ADAMTS19 polymorphisms associates with premature ovarian failure. Human Rep. 2013;28:3146-54. 15. Espey LL, Yoshioka S, Russell DL, Robker RL, Fuji S, Richards JS. Ovarian expression of a disintegrin and metalloproteinase with thrombospondin motifs during ovulation in the gonadotropin-primed immature rat. Biol Reprod 2000;62:1090–1095. 16. Richards JS, Hernandez-Gonzalez I, Gonzalez-Robayna I, Teuling E, Lo Y, Boerboom D, Falender AE, Doyle KH, LeBaron RG, Thompson V et al. Regulated expression of ADAMTS family members in follicles and cumulus oocyte complexes: evidence for specific and redundant patterns during ovulation. Biol Reprod 2005;72:1241–1255) 17. Kikuno R, Nagase T, Nakayama M, Koga H, Okazaki N, Nakajima D, Ohara O. HUGE: a database for human KIAA proteins, a 2004 update integrating HUGEppi and ROUGE. Nucleic Acids Res 2004;32:D502–D504) 18. Freimann S, Ben-Ami I, Dantes A, Armon L, Ben Ya'cov-Klein A, Ron-El R, et al. Differential expression of genes coding for EGF-like factors and ADAMTS1 following gonadotropin stimulation in normal and transformed human granulosa cells. Biochem Biophys Res Commun 2005;333:935–43. 19. Russell DL, Doyle KMH, Ochsner SA, Sandy JD, Richards JS. Processing and localization of ADAMTS-1 and proteolytic cleavage of versican during cumulus matrix expansion and ovulation. J Biol Chem 2003b;278: 42330–42339. 20. Ress D.G., 1987. Foundations of Statistics, Chapman and Hall, NewYork. 21. Doyle KM, Russell DL, Sriraman V, Richards JS. Coordinate transcription of the ADAMTS-1 gene by luteinizing hormone and progesterone receptor. Mol Endocrinol 2004;18:2463–78.) 22. Shindo T, Kurihara H, Kuno K, Yokoyama H, Wada T, Kurihara Y, et al. ADAMTS-1: a metalloproteinase-disintegrin essential for nor¬mal growth, fertility, and organ morphology and function. J Clin Invest 2000;105:1345-52. 23. Jung-A Pyun, Sunshin Kim, KyuBum Kwack. Interaction between thyroglobulin and ADAMTS16 in premature ovarian failure. Clin Exp Reprod Med 2014;41(3):120-124 24. Willis EL, Bridges PJ, Fortune JE. Progesterone receptor and prostaglandins mediate luteinizing hormone-induced changes in messenger RNAs for ADAMTS proteases in theca cells of bovine periovulatory follicles. Mol Reprod Dev. 2016 Nov 23. doi: 10.1002/mrd.22761.
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Articles |
| Authors | |
| Project Number | AR-1510 |
| Publication Date | June 15, 2020 |
| Submission Date | May 5, 2020 |
| Published in Issue | Year 2020 Volume: 10 Issue: 2 |
The published articles in SMJ are licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.