TAVŞANLARDA GEBELİK SONLANDIRMADA AGLEPRİSTON KULLANIMI

Serdal Kurt; Seçkin Salar

doi:10.33483/jfpau.498701

Review

TAVŞANLARDA GEBELİK SONLANDIRMADA AGLEPRİSTON KULLANIMI

Year 2019, Volume: 43 Issue: 2, 164 - 172, 01.06.2019

Serdal Kurt , Seçkin Salar

https://doi.org/10.33483/jfpau.498701

Abstract

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.

Keywords

aglepriston, gebelik, progesteron, tavşan

References

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).

AGLEPRISTONE USE FOR TERMINATION OF PREGNANCY IN RABBITS

Year 2019, Volume: 43 Issue: 2, 164 - 172, 01.06.2019

Serdal Kurt , Seçkin Salar

https://doi.org/10.33483/jfpau.498701

Abstract

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

References

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).

There are 32 citations in total.

Details

Primary Language	Turkish
Subjects	Pharmacology and Pharmaceutical Sciences
Journal Section	Collection
Authors	Serdal Kurt 0000-0002-0191-3245 Seçkin Salar 0000-0001-9303-6253
Publication Date	June 1, 2019
Submission Date	December 17, 2018
Acceptance Date	February 8, 2019
Published in Issue	Year 2019 Volume: 43 Issue: 2

Cite

APA	Kurt, S., & Salar, S. (2019). TAVŞANLARDA GEBELİK SONLANDIRMADA AGLEPRİSTON KULLANIMI. Journal of Faculty of Pharmacy of Ankara University, 43(2), 164-172. https://doi.org/10.33483/jfpau.498701
AMA	Kurt S, Salar S. TAVŞANLARDA GEBELİK SONLANDIRMADA AGLEPRİSTON KULLANIMI. J. Fac. Pharm. Ankara. June 2019;43(2):164-172. doi:10.33483/jfpau.498701
Chicago	Kurt, Serdal, and Seçkin Salar. “TAVŞANLARDA GEBELİK SONLANDIRMADA AGLEPRİSTON KULLANIMI”. Journal of Faculty of Pharmacy of Ankara University 43, no. 2 (June 2019): 164-72. https://doi.org/10.33483/jfpau.498701.
EndNote	Kurt S, Salar S (June 1, 2019) TAVŞANLARDA GEBELİK SONLANDIRMADA AGLEPRİSTON KULLANIMI. Journal of Faculty of Pharmacy of Ankara University 43 2 164–172.
IEEE	S. Kurt and S. Salar, “TAVŞANLARDA GEBELİK SONLANDIRMADA AGLEPRİSTON KULLANIMI”, J. Fac. Pharm. Ankara, vol. 43, no. 2, pp. 164–172, 2019, doi: 10.33483/jfpau.498701.
ISNAD	Kurt, Serdal - Salar, Seçkin. “TAVŞANLARDA GEBELİK SONLANDIRMADA AGLEPRİSTON KULLANIMI”. Journal of Faculty of Pharmacy of Ankara University 43/2 (June 2019), 164-172. https://doi.org/10.33483/jfpau.498701.
JAMA	Kurt S, Salar S. TAVŞANLARDA GEBELİK SONLANDIRMADA AGLEPRİSTON KULLANIMI. J. Fac. Pharm. Ankara. 2019;43:164–172.
MLA	Kurt, Serdal and Seçkin Salar. “TAVŞANLARDA GEBELİK SONLANDIRMADA AGLEPRİSTON KULLANIMI”. Journal of Faculty of Pharmacy of Ankara University, vol. 43, no. 2, 2019, pp. 164-72, doi:10.33483/jfpau.498701.
Vancouver	Kurt S, Salar S. TAVŞANLARDA GEBELİK SONLANDIRMADA AGLEPRİSTON KULLANIMI. J. Fac. Pharm. Ankara. 2019;43(2):164-72.

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The Journal of Faculty of Pharmacy of Ankara University is an international medium, an open access, peer-reviewed journal for the publication of original research reports, reviews and short communications in English or Turkish on relevant developments in pharmaceutical sciences., Proceeding of scientific meetings may be published as special issues of supplements to the journal. Additionally, it contains previous and forthcoming national and international scientific meetings with social activities in pharmaceutical areas.