Expression Profile of Prostaglandin Enzymes in Cystic Endometrial Hyperplasia in Dogs: The Results of a Hypothesis in Clinical Trial
Yıl: 2023 Cilt: 29 Sayı: 1 Sayfa Aralığı: 21 - 31 Metin Dili: İngilizce DOI: 10.9775/kvfd.2022.28403 İndeks Tarihi: 03-05-2023
Expression Profile of Prostaglandin Enzymes in Cystic Endometrial Hyperplasia in Dogs: The Results of a Hypothesis in Clinical Trial
Öz: Abstract: The expressions of prostaglandin synthesis enzymes and estrogen, progesterone receptors in canine cystic endometrial hyperplasia (CEH) were reported in this manuscript. Uterine tissue samples were collected from bitches with CEH (n=5), CEH-P (Cystic endometrial hyperplasia-Pyometra) (n=5) and healthy-negative control group, CG (n=5). Immunohistochemistry was carried out for the estrogen (ER) and progesterone receptor (PR) detection. Shock-frozen samples were utilized in mRNA extraction and Real-Time PCR was performed. Gene expression of PTGS2/COX2, PTGES, PTGER4, PGFS, PTGFR and PGR were detected higher in the CEH group compared with CG. The PGFS and PTGFR (FP) mRNA expressions were significantly increased in CEH compared with other groups. Expression of progesterone receptor mRNA (PGR) was highest in CEH and statistically different from the CEH-P group (P<0.05). No PR immunostaining was observed. ER staining had been detected in endometrial glands, endometrial stoma and myometrium, however hyperplasic glands in propria mucosa had lower or no ER scores. Based on the results of this study, the high levels of prostaglandin enzymes and low ER scores in CEH could be a preliminary step for the next stages of severe differentiation of endometrium.
Anahtar Kelime: Köpeklerde Kistik Endometriyal Hiperplazide Prostaglandin Enzimlerinin Ekspresyon Profili: Klinik Deneylerde Bir Hipotezin Sonuçları
Öz: Öz: Bu çalışmada köpek kistik endometriyal hiperplazi (KEH)’de prostaglandin sentez enzimleri, östrojen ve progesterone reseptörlerinin ekspresyonları rapor edilmiştir. Uterus örnekleri KEH (n=5) ve KEH-P (Kistik endomteriyal hiperplazi- pyometra) (n=5)’lı köpeklerden ve sağlıklı negatif kontrol köpeklerinden CG (n=5) toplanmıştır. Östrojen (ER) ve progesterone (PR) reseptörü belirlenmesi için immunohistokimya kullanılmıştır. Şok dondurulan doku örnekleri mRNA ekstraksiyonunda kullanılmış ve bu örneklerden Real Time PCR yapılmıştır. PTGS2/COX2, PTGES, PTGER4, PGFS, PTGFR ve PGR gen ekspresyonu KEH’de, kontrol grubuna göre yüksek bulunmuştur. PGFS ve PTGFR (FP) mRNA ekspresyonları KEH grubunda diğer gruplara göre istatistiksel olarak farklı bulunmuştur. Progesterone reseptor mRNA (PGR) ekspresyonu KEH’de en yüksek ve KEH-P grubuna göre farklı bulunmuştur (P<0.05). PR immun boyamada belirlenememiştir. ER boyanmaları ise endometriyal bezler, endometriyal stroma ve miyometriyumda gözlenirken, proprio mukozadaki hiperplastik bezlerde ya çok az boyanmış ya da hiç boyanma gözlenmemiştir. Bu çalışmanın sonuçlarına dayanarak, CEH’deki yüksek prostaglandin enzim seviyeleri ve düşük ER skorları, endometriumun şiddetli farklılaşmasının sonraki aşamaları için öncü bir adım olabilir.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
- 1. Schlafer DH, Gifford AT: Cystic endometrial hyperplasia, pseudoplacentational endometrial hyperplasia, and other cystic conditions of the canine and feline uterus. Theriogenology, 70 (3): 349-358, 2008. DOI: 10.1016/j.theriogenology.2008.04.041
- 2. Verstegen J, Dhaliwal G, Verstegen-Onclin K: Mucometra, cystic endometrial hyperplasia, and pyometra in the bitch: Advances in treatment and assessment of future reproductive success. Theriogenology, 70 (3): 364- 374, 2008. DOI: 10.1016/j.theriogenology.2008.04.036
- 3. De Bosschere H, Ducatelle R, Vermeirsch H, Van Den Broeck W, Coryn M: Cystic endometrial hyperplasia-pyometra complex in the bitch: Should the two entities be disconnected? Theriogenology, 55 (7): 1509-1519, 2001. DOI: 10.1016/s0093-691x(01)00498-8
- 4. Kim KS, Kim O: Cystic endometrial hyperplasia and endometritis in a dog following prolonged treatment of medroxyprogesterone acetate. J Vet Sci, 6 (1): 81-82, 2005.
- 5. Tavares WLF, Lavalle GE, Figueiredo MS, Souza AG, Bertagnolli AC, Viana FAB, Paes PRO, Carneiro RA, Cavalcanti GAO, Melo MM, Cassali GD: Evaluation of adverse effects in tamoxifen exposed healthy female dogs. Acta Vet Scand, 52 (1): 67, 2010. DOI: 10.1186/1751-0147-52-67
- 6. Nomura K: Canine pyometra with cystic endometrial hyperplasia experimentally induced by E. coli inoculation. Nihon Juigaku Zasshi, 45 2): 237-240, 1983. DOI: 10.1292/jvms1939.45.237
- 7. Dhaliwal GK, England GC, Noakes DE: The effects of endometrial scarification on uterine steroid receptors, bacterial flora and histological structure in the bitch. Anim Reprod Sci, 69 (3-4): 239-249, 2002. DOI: 10.1016/s0378-4320(01)00183-x
- 8. Aflatoonian R, Tuckerman E, Elliott SL, Bruce C, Aflatoonian A, Li TC, Fazeli A: Menstrual cycle-dependent changes of Toll-like receptors in endometrium. Hum Reprod, 22 (2): 586-593, 2007. DOI: 10.1093/humrep/del388
- 9. Silva E, Henriques S, Brito S, Ferreira-Dias G, Lopes-da-Costa L, Mateus L: Oestrous cycle-related changes in production of Toll-like receptors and prostaglandins in the canine endometrium. J Reprod Immunol, 96 (1-2): 45-57, 2012. DOI: 10.1016/j.jri.2012.07.003
- 10. Rocca B, FitzGerald G: Cyclooxygenases and prostaglandins: shaping up the immune response. Int Immunopharmacol, 2 (5): 603-630, 2002. DOI: 10.1016/s1567-5769(01)00204-1
- 11. Silva E, Leitão S, Henriques S, Kowalewski MP, Hoffmann B, Ferreira- Dias G, da Costa LL, Mateus L: Gene transcription of TLR2, TLR4, LPS ligands and prostaglandin synthesis enzymes are up-regulated in canine uteri with cystic endometrial hyperplasia-pyometra complex. J Reprod Immunol, 84 (1): 66-74, 2010. DOI: 10.1016/j.jri.2009.10.004
- 12. Dvorak HF. Tumors: Wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med, 315 (26): 1650- 1659, 1986. DOI: 10.1056/NEJM198612253152606
- 13. Badawi AF. The role of prostaglandin synthesis in prostate cancer. BJU Int, 85 (4): 451-462, 2000. DOI: 10.1046/j.1464-410x.2000.00507.x
- 14. Dore M: Cyclooxygenase-2 expression in animal cancers. Vet Pathol, 48 (1): 254-265, 2011. DOI: 10.1177/0300985810379434
- 15. Kalinski P: Regulation of immune responses by prostaglandin E2. J Immunol, 188 (1): 21-28, 2012. DOI: 10.4049/jimmunol.1101029
- 16. Szweda M, Rychlik A, Babińska I, Pomianowski A: Significance of cyclooxygenase-2 in oncogenesis. J Vet Res, 63 (2): 215-224, 2019. DOI: 10.2478/jvetres-2019-0030
- 17. Tong D, Liu Q, Wang LA, Xie Q, Pang J, Huang Y, Wang L, Liu G, Zhang D, Lan W, Jiang J: The roles of the COX2/PGE2/EP axis in therapeutic resistance. Cancer Metastasis Rev, 37 (2-3): 355-368, 2018. DOI: 10.1007/s10555-018-9752-y
- 18. Zhu J: The expression of prostaglandin E receptors and their roles in healthy and diseased endometrium. PhD Thesis, Ludwig-Maximilians- Universiy, Institute of Health Science, 2019.
- 19. Ye Y, Wang X, Jeschke U, von Schönfeldt V: COX 2 PGE2 EPs in gynecological cancers. Arch Gynecol Obstet, 301 (6): 1365-1375, 2020. DOI: 10.1007/s00404-020-05559-6
- 20. Nees LK, Heublein S, Steinmacher S, Juhasz-Böss I, Brucker S, Tempfer CB, Wallwiener M: Endometrial hyperplasia as a risk factor of endometrial cancer. Arch Gynecol Obstet, 306 (2): 407-421, 2022. DOI: 10.1007/s00404-021-06380-5
- 21. Cave TA, Hine R, Howie F, Thompson H, Argyle DJ: Uterine carcinoma in a 10-month-old golden retriever. J Small Anim Pract, 43 (3):133-135, 2002. DOI: 10.1111/j.1748-5827.2002.tb00044.x
- 22. Sapierzynski RA, Dolka I, Cywinska A: Multiple pathologies of the feline uterus: A case report. Vet Med, 52 (7): 345-350, 2009. DOI: 10.17221/101/2009-VETMED
- 23. Jankowski G, Adkesson MJ, Langan JN, Haskins S, Landolfi J: Cystic endometrial hyperplasia and pyometra in three captive African hunting dogs (Lycaon pictus). J Zoo Wildl Med, 43 (1): 95-100, 2012. DOI: 10.1638/2010-0222.1
- 24. Dow C: The cystic hyperplasia-pyometra complex in the bitch. J Comp Pathol, 69 (49): 237- 250, 1959. DOI: 10.1016/S0368-1742(59)80023-0
- 25. Munson L, Gardner IA, Masson RJ, Chassy LM, Seal US: Endometrial hyperplasia and mineralization in zoo felids treated with melengestrol acetate Contraceptives. Vet Pathol, 39 (4): 419-427, 2002. DOI: 10.1354/vp.39-4-419
- 26. Veiga GA, Miziara RH, Angrimani DS, Papa PC, Cogliati B, Vannucchi CI: Cystic endometrial hyperplasia-pyometra syndrome in bitches: identification of hemodynamic, inflammatory, and cell proliferation changes. Biol Reprod, 96 (1): 58-69, 2017. DOI: 10.1095/biolreprod.116.140780
- 27. Fulton AM, Ma X, Kundu N: Targeting prostaglandin E EP receptors to inhibit metastasis. Cancer Res, 66 (20): 9794-9797, 2006. DOI: 10.1158/0008- 5472.CAN-06-2067
- 28. Silva E, Leitao S, Ferreira-Dias G, Lopes da Costa L, Mateus L: Prostaglandin synthesis genes are differentially transcripted in normal and pyometra endometria of bitches. Reprod Domest Anim, 44 (2): 200-203, 2009. DOI: 10.1111/j.1439-0531.2009.01393.x
- 29. Singh LK, Patra MK, Mishra GK, Saxena AC, De UK, Singh SK, Kumar H, Narayanan K: Prospects of diagnostic and prognostic biomarkers of pyometra in canine. Asian Pac J Reprod, 9 (4): 166-173, 2020. DOI: 10.4103/2305-0500.288584
- 30. Wallace AE, Sales KJ, Catalano RD, Anderson RA, Williams AR, Wilson MR, Schwarze J, Wang H, Rossi AG, Jabbour HN: Prostaglandin F2a-F-prostanoid receptor signaling promotes neutrophil chemotaxis via chemokine (C-X-C motif) ligand 1 in endometrial adenocarcinoma. Cancer Res, 69 (14): 5726-5733, 2009. DOI: 10.1158/0008-5472.CAN-09- 0390
- 31. Rodenas C, Agut A, Bernabe A, Gómez MA, Lucas X: Endometrial mineralisation in a bitch with ovarian granulosa cell tumour and cystic endometrial hyperplasia-pyometra complex. Vet Rec Case Rep, 8:e000984, 2020. DOI: 10.1136/vetreccr-2019-000984
- 32. Marinković D, Aničić M, Vakanjac S, Nedić S, Magaš V: Morphological characteristics and expression of estrogen and progesterone receptors in the canine endometrium during the estrus cycle, cystic endometrial hyperplasia and pyometra. Acta Vet Belgrade, 68 (3): 239-250, 2018. DOI: 10.2478/acve- 2018-0021
- 33. Skrzypczak M, Merx I, Schüler-Toprak S, Weber F, Inwald EC, Ortmann O, Treeck O: Molecular profiling of estrogen receptor α and progesterone receptor transcript variants in endometrial cancer. Steroids, 104, 122-128, 2015. DOI: 10.1016/j.steroids.2015.09.004
- 34. Guil-Luna S, Stenvang J, Brünner N, De Andrés FJ, Rollón E, Domingo V, Sánchez-Céspedes R, Millán Y, Martín de Las Mulas J: Progesterone receptor isoform A may regulate the effects of neoadjuvant aglepristone in canine mammary carcinoma. BMC Vet Res, 10:296, 2014. DOI: 10.1186/ s12917-014-0296-2
- 35. Fabris V, Abascal MF, Giulianelli S, May M, Sequeira GR, Jacobsen B, Lombès M, Han J, Tran L, Molinolo A, Lanari C: Isoform specificity of progesterone receptor antibodies. J Pathol Clin Res, 3 (4): 227-233, 2017. DOI: 10.1002/cjp2.83
- 36. Samalecos A, Gellersen B: Systematic expression analysis and antibody screening do not support the existence of naturally occurring progesterone receptor (PR)-C, PR-M, or other truncated PR isoforms. Endocrinology, 149 (11): 5872-5887, 2008. DOI: 10.1210/en.2008-0602
- 37. Li Y, Yang D, Yin X, Zhang X, Huang J, Wu Y, Wang M, Yi Z, Li H, Li H, Ren G: Clinicopathological characteristics and breast cancer– specific survival of patients with single hormone receptor–positive breast cancer. JAMA Netw Open, 3 (1):e1918160, 2020. DOI: 10.1001/ jamanetworkopen.2019.18160
- 38. Brunetti B, Bacci B, Angeli C, Benazzi C, Muscatello LV: p53, ER, and Ki67 expression in canine mammary carcinomas and correlation with pathological variables and prognosis. Vet Pathol, 58 (2): 325-331, 2021. DOI: 10.1177/0300985820973462
| APA | KORLU Y, Yavas O, AKTAR A, Bozkurt B, ozyigit o, ozalp g (2023). Expression Profile of Prostaglandin Enzymes in Cystic Endometrial Hyperplasia in Dogs: The Results of a Hypothesis in Clinical Trial. , 21 - 31. 10.9775/kvfd.2022.28403 |
| Chicago | KORLU YEŞİM,Yavas Ozkan,AKTAR Ahmet,Bozkurt Berkay,ozyigit ozgur,ozalp gozde Expression Profile of Prostaglandin Enzymes in Cystic Endometrial Hyperplasia in Dogs: The Results of a Hypothesis in Clinical Trial. (2023): 21 - 31. 10.9775/kvfd.2022.28403 |
| MLA | KORLU YEŞİM,Yavas Ozkan,AKTAR Ahmet,Bozkurt Berkay,ozyigit ozgur,ozalp gozde Expression Profile of Prostaglandin Enzymes in Cystic Endometrial Hyperplasia in Dogs: The Results of a Hypothesis in Clinical Trial. , 2023, ss.21 - 31. 10.9775/kvfd.2022.28403 |
| AMA | KORLU Y,Yavas O,AKTAR A,Bozkurt B,ozyigit o,ozalp g Expression Profile of Prostaglandin Enzymes in Cystic Endometrial Hyperplasia in Dogs: The Results of a Hypothesis in Clinical Trial. . 2023; 21 - 31. 10.9775/kvfd.2022.28403 |
| Vancouver | KORLU Y,Yavas O,AKTAR A,Bozkurt B,ozyigit o,ozalp g Expression Profile of Prostaglandin Enzymes in Cystic Endometrial Hyperplasia in Dogs: The Results of a Hypothesis in Clinical Trial. . 2023; 21 - 31. 10.9775/kvfd.2022.28403 |
| IEEE | KORLU Y,Yavas O,AKTAR A,Bozkurt B,ozyigit o,ozalp g "Expression Profile of Prostaglandin Enzymes in Cystic Endometrial Hyperplasia in Dogs: The Results of a Hypothesis in Clinical Trial." , ss.21 - 31, 2023. 10.9775/kvfd.2022.28403 |
| ISNAD | KORLU, YEŞİM vd. "Expression Profile of Prostaglandin Enzymes in Cystic Endometrial Hyperplasia in Dogs: The Results of a Hypothesis in Clinical Trial". (2023), 21-31. https://doi.org/10.9775/kvfd.2022.28403 |
| APA | KORLU Y, Yavas O, AKTAR A, Bozkurt B, ozyigit o, ozalp g (2023). Expression Profile of Prostaglandin Enzymes in Cystic Endometrial Hyperplasia in Dogs: The Results of a Hypothesis in Clinical Trial. Kafkas Üniversitesi Veteriner Fakültesi Dergisi, 29(1), 21 - 31. 10.9775/kvfd.2022.28403 |
| Chicago | KORLU YEŞİM,Yavas Ozkan,AKTAR Ahmet,Bozkurt Berkay,ozyigit ozgur,ozalp gozde Expression Profile of Prostaglandin Enzymes in Cystic Endometrial Hyperplasia in Dogs: The Results of a Hypothesis in Clinical Trial. Kafkas Üniversitesi Veteriner Fakültesi Dergisi 29, no.1 (2023): 21 - 31. 10.9775/kvfd.2022.28403 |
| MLA | KORLU YEŞİM,Yavas Ozkan,AKTAR Ahmet,Bozkurt Berkay,ozyigit ozgur,ozalp gozde Expression Profile of Prostaglandin Enzymes in Cystic Endometrial Hyperplasia in Dogs: The Results of a Hypothesis in Clinical Trial. Kafkas Üniversitesi Veteriner Fakültesi Dergisi, vol.29, no.1, 2023, ss.21 - 31. 10.9775/kvfd.2022.28403 |
| AMA | KORLU Y,Yavas O,AKTAR A,Bozkurt B,ozyigit o,ozalp g Expression Profile of Prostaglandin Enzymes in Cystic Endometrial Hyperplasia in Dogs: The Results of a Hypothesis in Clinical Trial. Kafkas Üniversitesi Veteriner Fakültesi Dergisi. 2023; 29(1): 21 - 31. 10.9775/kvfd.2022.28403 |
| Vancouver | KORLU Y,Yavas O,AKTAR A,Bozkurt B,ozyigit o,ozalp g Expression Profile of Prostaglandin Enzymes in Cystic Endometrial Hyperplasia in Dogs: The Results of a Hypothesis in Clinical Trial. Kafkas Üniversitesi Veteriner Fakültesi Dergisi. 2023; 29(1): 21 - 31. 10.9775/kvfd.2022.28403 |
| IEEE | KORLU Y,Yavas O,AKTAR A,Bozkurt B,ozyigit o,ozalp g "Expression Profile of Prostaglandin Enzymes in Cystic Endometrial Hyperplasia in Dogs: The Results of a Hypothesis in Clinical Trial." Kafkas Üniversitesi Veteriner Fakültesi Dergisi, 29, ss.21 - 31, 2023. 10.9775/kvfd.2022.28403 |
| ISNAD | KORLU, YEŞİM vd. "Expression Profile of Prostaglandin Enzymes in Cystic Endometrial Hyperplasia in Dogs: The Results of a Hypothesis in Clinical Trial". Kafkas Üniversitesi Veteriner Fakültesi Dergisi 29/1 (2023), 21-31. https://doi.org/10.9775/kvfd.2022.28403 |
