Mehmet Sühha BOSTANCI, Gürkan DEMİR, Ayça Taş TUNA, Özcan BUDAK, Havva KOÇYİĞİT, Berrin GÜNAYDIN, Hüseyin ÇAKIROĞLU

Propofol, Deksmedetomidin ve Medetomidinin Sıçanlarda Oosit Kümülüs Granulosa Hücreleri Üzerine Apoptotik Etkilerinin Araştırılması

Amaç: Oosit toplama işlemi sırasında kullanılan propofol, deks- medetomidin ve medetomidinin kümülüs hücreleri üzerindeki po- tansiyel apoptotik etkilerini rat ovulasyon indüksiyon modelinde değerlendirmeyi amaçladık. Yöntem: Ovulasyon indüksiyon modeli oluşturulduktan sonra, sı- çanlara Grup D’de deksmedetomidin, Grup P’de propofol, Grup M’de medetomidin verildi. Çalışma ilaçlarının uygulanmasından 10 dakika sonra oosit toplama işlemi yapıldı. Kaspaz-3 immunohis- tokimyasal değerlendirmede rastgele seçilen beş alanda boyanma düzeyi skorlandı ve en yüksek skora sahip alanlar belirlendi. Her bölüm için immünohistokimyasal boyama puanlaması, H-skoru adı verilen bir puanlama algoritması kullanılarak yapıldı. Bulgular: Kümülüs hücrelerinde kaspaz-3 ekspresyonu Grup D’de en düşük, Grup P’de en yüksek bulundu. Ortalama kaspaz-3 H-sko- ru Grup D’de Grup P ve M’ye göre daha düşüktü (p

Investigation of Apoptotic Effect of Propofol, Dexmedetomidine and Medetomidine on Oocyte Cumulus Granulosa Cells in Rats

Objective: We aimed to evaluate the potential apoptotic effects of propofol, dexmedetomidine and medetomidine that were used during oocyte retrieval on cumulus cells in rat ovulation induction model. Methods: After the ovulation induction model was created, rats were received dexmedetomidine in Group D, propofol in Group P, medetomidine in Group M. Oocytes collection was performed 10 minutes after the administration of study drugs. For Caspase-3 immunohistochemical evaluation, the staining level was scored in five randomly selected areas and the areas with the highest score were determined. Immunohistochemical staining scoring for each section was performed using a scoring algorithm called H-score. Results: Caspase-3 expression in cumulus cells was found to be lowest in Group D and highest in Group P. The mean caspase-3 H-score was lower in Group D than that of Group P and M (p

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1. Tobias JD, Leder M. Procedural sedation: A review of sedative agents, monitoring, and management of complications. Saudi J Anaesth 2011;5(4):395-410.
2. Christiaens F, Janssenswillen C, Verborgh C et al. Propofol concentrations in follicular fluid during general anaesthesia for transvaginal oocyte retrieval. Hum Reprod 1999;14(2):345-8.
3. Coskun D, Gunaydin DB, Tas Tuna A, Celebi HS, Kaya K, Erdem A. Bolus fentanyl coadministered with target controlled infusion of propofol infusion of propofol for oocyte retrieval. J Reproductive Med 2017;62(11-12):641-6.
4. Elsersi MH, Abuelghar WM, Makled AK. The emergence profile of propofol sedation compared with dexmedetomidine injection during ultrasound-guided oocyte pickup for in-vitro fertilization. Ain-Shams J Anaesthesiol 2015;8(3):327-33.
5. Ali Elnabtity AM, Selim MF. A prospective randomized trial comparing dexmedetomidine and midazolam for conscious sedation during oocyte retrieval in an in vitro fertilization program. Anesth Essays Res 2017;11(1):34-9.
6. Jang HS, Lee MG. Effects of medetomidine on analgesia and sedation in rats. J Vet Clin 2010;27(6):674-8.
7. Yuan YQ, Van Soom A, Leroy JLMR, et al. Apoptosis in cumulus cells, but not in oocytes, may influence bovine embryonic developmental competence. Theriogenology 2005;63(8):2147-63.
8. Hino C, Ueda J, Funakoshi H, Matsumoto S. Defined oocyte collection time is critical for reproducible in vitro fertilization in rats of different strains. Theriogenology 2020;144:146-51.
9. Celik S, Ozkavukcu S, Celik-Ozenci C. Altered expression of activator proteins that control follicle reserve after ovarian tissue cryopreservation/transplantation and primordial follicle loss prevention by rapamycin. J Assist Reprod Genet 2020;37(9):2119-36.
10. Smith SD, Mikkelsen A, Lindenberg S. Development of human oocytes matured in vitro for 28 or 36 hours. Fertil Steril 2000;73(3):541-4.
11. Zang L, Zhang Q, Zhou Y, et al. Expression pattern of G protein-coupled estrogen receptor 1 (GPER) in human cumulus granulosa cells (CGCs) of patients with PCOS. Syst Biol Reprod Med 2016;62(3):184-91.
12. Nakahara K, Saito H, Saito T, et al. The incidence of apoptotic bodies in membrana granulosa can predict prognosis of ova from patients participating in in vitro fertilization programs. Fertil Steril 1997;68(2):312-7.
13. Høst E, Mikkelsen AL, Lindenberg S, Smidt-Jensen S. Apoptosis in human cumulus cells in relation to maturation stage and cleavage of the corresponding oocyte. Acta Obstet Gynecol Scand 2000;79(11):936-40.
14. Raman RS, Chan PJ, Corselli JU, et al. Comet assay of cumulus cell DNA status and the relationship to oocyte fertilization via intracytoplasmic sperm injection. Hum Reprod 2001;16(5):831-5.
15. Jacobson MD, Weil M, Raff MC. Programmed cell death in animal development. Cell 1997;88(3):347-54.
16. Saraste A, Pulkki K. Morphologic and biochemical hallmarks of apoptosis. Cardiovasc Res 2000;45(3):528-37.
17. Haouzi D, Hamamah S. Pertinence of apoptosis markers for the improvement of in vitro fertilization (IVF). Curr Med Chem 2009;16(15):1905-16.
18. Malviya S, Voepel-Lewis T, Tait AR. Adverse events and risk factors associated with the sedation of children by non- anesthesiologists. Anesth Analg 1997;85(6):1207-13.
19. Lin D, Ran J, Zhu S, et al. Effect of GOLPH3 on cumulus granulosa cell apoptosis and ICSI pregnancy outcomes. Sci Rep 2017;7(1):7863.
20. Kang FC, Chen YC, Wang SC, So EC, Huang BM. Propofol induces apoptosis by activating caspases and the MAPK pathways, and inhibiting the Akt pathway in TM3 mouse Leydig stem/progenitor cells. Int J Mol Med 2020;46(1):439- 48.
21. Kang FC, Wang SC, So EC, et al. Propofol may increase caspase and MAPK pathways, and suppress the Akt pathway to induce apoptosis in MA-10 mouse Leydig tumor cells. Oncol Rep 2019;41(6):3565-74.
22. Budak O, Bostancı MS, Tuna A, Toprak V, Cakiroglu H, Gok K. The effect of Propofol versus Dexmedetomidine as anesthetic agents for oocyte pick-up on in vitro fertilization (IVF) outcomes. Sci Rep 2021;11(1):23922.
23. Duan XG, Huang ZQ, Hao CG, et al. The role of propofol on mouse oocyte meiotic maturation and early embryo development. Zygote 2018;26(4):261-9.
24. Cai Y, Xu H, Yan J, Zhang L, Lu Y. Molecular targets and mechanism of action of dexmedetomidine in treatment of ischemia/reperfusion injury. Mol Med Rep 2014;9(5):1542- 50.
25. Zhai M, Liu C, Li Y, et al. Dexmedetomidine inhibits neuronal apoptosis by inducing Sigma-1 receptor signaling in cerebral ischemia-reperfusion injury. Aging (Albany NY) 2019;11(21):9556-68.
26. Cekic B, Besir A, Yulug E, Geze S, Alkanat M. Protective effects of dexmedetomidine in pneumoperitoneum-related ischaemia-reperfusion injury in rat ovarian tissue. Eur J Obstet Gynecol Reprod Biol 2013;169(2):343-6.
27. Sinclair MD. A review of the physiological effects of alpha2- agonists related to the clinical use of medetomidine in small animal practice. Can Vet J 2003;44(11):885-97.
28. Madrigal-Valverde M, Bittencourt RF, Ribeiro Filho AD, et al. Quality of domestic cat semen collected by urethral catheterization after the use of different alpha 2-adrenergic agonists. J Feline Med Surg 2021;23(8):745-50.