TAVŞANLARDA GEBELİK SONLANDIRMADA AGLEPRİSTON KULLANIMI

Amaç: Tavşanlarda gebeliğin sonlandırılmasında aglepriston kullanımın araştırılması. Aglepriston (RU 46534) progesteron (P4) antagonisti olan sentetik yapılı steroid hormondur. Birçok hayvan türünde olduğu gibi tavşanlarda da istenmeyen gebeliklerin sonlandırılmasında kullanılmaktadır. Tavşanlarda gebeliğin devamlılığından sorumlu primer hormon P4 dür. Aglepriston tavşanlarda progesteron reseptörlerine (PR) P4’den 3,8 kat daha hızlı bağlanmaktadır. Bu nedenle gebelik sonlandırmada %100 başarı sağlamaktadır. Etkin dozu 10mg/kg 24 saat arayla iki kez ve uygulama yolu subcutan olarak belirtilmiştir. Tavşanlarda gebeliğin 5-6 gününden 15. gününe kadar kullanılması uygundur. Aglepriston erken dönem gebeliğin sonlandırılmasında kullanıldığında embriyo rezorbe olarak vajinal kanama ve akıntı oluşmadığı bildirilmiştir. Ancak orta dönem gebelikleri sonlandırma uygulamalarında fetüsün atılıp kanlı vajinal akıntının oluştuğu görülmüştür. Ayrıca sonraki dönemlerde fertilite parametrelerinde anlamlı bir farklılık görülmezken her iki dönem uygulamalarında da düzensiz çiftleşme eğilimi ile beraber doğum gebe kalma aralığının uzadığı olgular tespit edilmiştir. Bunun yanında sitotoksik, genotoksik etkileri ve bazı hemotolojik parametrelerde değişimlere neden olduğu anlaşıldı. Sonuç ve Tartışma: Aglepristonun tedavi başarısızlığı henüz bildirilmemiş olmasına rağmen gebelik sonlandırmadaki etkisinin yanında maternal değişimler üzerine hematolojik düzeyde etkisinin araştırılmasının önemli olacağı düşünüldü.

AGLEPRISTONE USE FOR TERMINATION OF PREGNANCY IN RABBITS

Objective: It is the investigation of aglepriston use in termination of pregnancy in the rabbits. Aglepriston (RU 46534) is a synthetic steroid hormone that is progesterone (P4) antagonist. It is used to terminate unwanted pregnancies in many animal species including rabbits. The P4 is primary hormone that is responsible for maintain of pregnancy in rabbits. Its affinity to PR is 3.8 times higher than P4 and so eliminates effect of P4. Therefore, aglepristone is provide 100% success in termination of pregnancy. The effective dose is 10 mg/kg subcutan twice 24 hours apart. It is suitable period for treatment between 5-6th and 15th days of pregnancy in rabbits. It was reported that when aglepristone was used to terminate early pregnancy, vaginal bleeding and discharge didn’t occur and it resulted in embryo resorption. But, in midpregnancy applications, it was recorded that resulted in fetal expulsion and vaginal bleeding and discharge were occured. In addition, it was stated that there was no significant difference in subsequent fertility parameters. But, in both applications, it was determined that irregular mating behavior and parturition to pregnancy interval extend. Besides, it was understood that aglepristone caused cytotoxic, genotoxic effects and changes in some hematological parameters in rabbits.Result and Discussion: Although the treatment failure of agleprolone has not been reported yet, It was thought that it would be important to investigate toxic effects at the cellular level on maternal changes in addition to the effect of pregnancy termination. Sonuç ve Tartışma: Aglepristonun tedavi başarısızlığı henüz bildirilmemiş olmasına rağmen gebelik sonlandırmadaki etkisinin yanında maternal değişimler üzerine hematolojik düzeyde etkisinin araştırılmasının önemli olacağı düşünüldü.

Keywords:

aglepriston, pregnancy progesterone, rabbit,

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1. Hoffmann, B., & Schuler, G. (2000). Receptor blockers—general aspects with respect to their use in domestic animal reproduction. Animal reproduction science, 60, 295-312.
2. Baan, M., Taverne, M. A. M., Kooistra, H. S., De Gier, J., Dieleman, S. J., & Okkens, A. C. (2005). Induction of parturition in the bitch with the progesterone-receptor blocker aglepristone. Theriogenology, 63(7), 1958-1972.
3. PubChem web site. (2018). Retrieved November 19, 2018, from https://pubchem.ncbi.nlm.nih.gov/compound/Aglepristone#section=Top
4. Jurka, P., Szulc-Dąbrowska, L., Borkowska, J., & Winnicka, A. (2013). Lack of in vitro effect of aglepristone on IFN-γ and IL-4 production by resting and mitogen-activated T cells of luteal bitches. BMC veterinary research, 9(1), 220.
5. Gobello, C. (2006). Dopamine agonists, anti-progestins, anti-androgens, long-term-release GnRH agonists and anti-estrogens in canine reproduction: A review. Theriogenology, 66(6-7), 1560-1567.
6. Chesler, E. J., & Juraska, J. M. (2000). Acute administration of estrogen and progesterone impairs the acquisition of the spatial Morris water maze in ovariectomized rats. Hormones and behavior, 38(4), 234-242.
7. Mulac-Jericevic, B., & Conneely, O. M. (2004). Reproductive tissue selective actions of progesterone receptors. Reproduction, 128(2), 139-146.
8. Arck, P., Hansen, P. J., Mulac Jericevic, B., Piccinni, M. P., & Szekeres‐Bartho, J. (2007). Progesterone during pregnancy: endocrine–immune cross talk in mammalian species and the role of stress. American journal of reproductive immunology, 58(3), 268-279.
9. Parillo, F., Dall’Aglio, C., Brecchia, G., Maranesi, M., Polisca, A., Boiti, C., & Zerani, M. (2013). Aglepristone (RU534) effects on luteal function of pseudopregnant rabbits: steroid receptors, enzymatic activities, and hormone productions in corpus luteum and uterus. Animal reproduction science, 138(1-2), 118-132.
10. Gogny, A., & Fiéni, F. (2016). Aglepristone: A review on its clinical use in animals. Theriogenology, 85(4), 555-566.
11. Szendrő, Z., Szendrő, K., & Dalle Zotte, A. (2012). Management of reproduction on small, medium and large rabbit farms: a review. Asian-Australasian journal of animal sciences, 25(5), 738.
12. Bishop, C. R. (2002). Reproductive medicine of rabbits and rodents. The veterinary clinics of North America. Exotic animal practice, 5(3), 507-35.
13. Geyer, A., Daub, L., Otzdorff, C., Reese, S., Braun, J., & Walter, B. (2016). Reversible estrous cycle suppression in prepubertal female rabbits treated with slow-release deslorelin implants. Theriogenology, 85(2), 282-287.
14. Harcourt-Brown, F. M. (2017). Disorders of the Reproductive Tract of Rabbits. Veterinary Clinics: Exotic Animal Practice, 20(2), 555-587.
15. YoungLai, E. V., Thompson, N., & Foster, W. (1989). Effects of in-vivo administration of GnRH on the release of gonadotrophins in the female rabbit. Journal of reproduction and fertility, 85(1), 325-329.
16. Saeed, A. M., Jiménez, F. M., & Vicente, J. S. (2015). Oviductal and endometrial mRNA expression of implantation candidate biomarkers during early pregnancy in rabbit. Zygote, 23(2), 288-296.
17. El-Gayar, M., Khalil, H., Hanafy, A., Yaseen, M., Hegaze, E., Marthold, D., ... & Holtz, W. (2014). Pregnancy detection in rabbits by ultrasonography as compared to manual palpation. Egyptian J. Anim. Prod, 51(3), 196-199.
18. Yakovleva, A. A., Nazarova, L. A., Prokopenko, V. M., & Pavlova, N. G. (2017). Effect of Tramadol on Rabbit Uterine Contractile Activity Induced in Late Pregnancy. Bulletin of experimental biology and medicine, 162(3), 349-352.
19. Blanks, A. M., & Thornton, S. (2003). The role of oxytocin in parturition. BJOG: An International Journal of Obstetrics & Gynaecology, 110, 46-51.
20. González-Mariscal, G. A. B. R. I. E. L. A. (2004, September). Maternal behaviour in rabbits: regulation by hormonal and sensory factors. In Proc. 8th World Rabbit Congr., Puebla, Mexico (pp. 1218-1228).
21. Garfield, R. E., Saade, G., & Chwalisz, K. (1998). Endocrine control of parturition. In Endocrinology of pregnancy (pp. 407-430). Humana Press, Totowa, NJ.
22. González-Mariscal, G., Díaz-Sánchez, V., Melo, A. I., Beyer, C., & Rosenblatt, J. S. (1994). Maternal behavior in New Zealand white rabbits: quantification of somatic events, motor patterns, and steroid plasma levels. Physiology & behavior, 55(6), 1081-1089.
23. González-Mariscal, G., Caba, M., Martínez-Gómez, M., Bautista, A., & Hudson, R. (2016). Mothers and offspring: the rabbit as a model system in the study of mammalian maternal behavior and sibling interactions. Hormones and Behavior, 77, 30-41.
24. Oguejiofor, C. F., and I. S. Ochiogu, I. S. (2013). Prolonged interval before conception following aglepristone-induced abortion in albino rats. Anim Reprod 10, 41-4.
25. Galac, S., Kooistra, H. S., Dieleman, S. J., Cestnik, V., & Okkens, A. C. (2004). Effects of aglepristone, a progesterone receptor antagonist, administered during the early luteal phase in non-pregnant bitches. Theriogenology, 62(3-4), 494-500.
26. Marcinkiewicz, J. L., & Bahr, J. M. (1993). Identification and preliminary characterization of luteotropic activity in the rabbit placenta. Biology of reproduction, 48(2), 403-408.
27. Chang, C. C., Wang, W. C., & Bardin, C. W. (1993). Termination of early pregnancy in the rat, rabbit, and hamster with RU 486 and anordrin. Contraception, 47(6), 597-608.
28. Özalp, G. R., Çalışkan, Ç., Seyrek‐İntaş, K., & Wehrend, A. (2010). Effects of the progesterone receptor antagonist aglepristone on implantation administered on days 6 and 7 after mating in rabbits. Reproduction in domestic animals, 45(3), 505-508.
29. Özalp, G. R., Seyrek-Intaş, K., Çalışkan, Ç., & Wehrend, A. (2008). Mid-gestation pregnancy termination in rabbits by the progesterone antagonist aglepristone. Theriogenology, 69(9), 1056-1060.
30. Özalp, G. R., Temizel, E. M., & Özocak-Batmaz, E. (2013). Clinical, ultrasonography and haematology of aglepristone-induced mid-gestation pregnancy terminations in rabbits. Journal of the South African Veterinary Association, 84(1), 00-00.
31. Vatan, Ö., Bagdas, D., Cinkilic, N., Wehrend, A., Özalp, GR. (2015). Genotoxic and cytotoxic effects of the aglepristone, a progesteron antagonist, in mid-gestation pregnancy termination in rabbits. Kafkas Univ Vet Fak Derg, 21 (2): 241-246.
32. SONAT, F. A., Bağdaş, D., Zülfiye, G. Ü. L., & Özalp, G. R. (2013). Tavşanlarda Orta Dönem Gebeliklerin Sonlandırılmasında Kullanılan Aglepriston'un Bazı Oksidatif Stres Parametreleri Üzerine Etkisi. Uludağ Üniversitesi Veteriner Fakültesi Dergisi, 32(2).