Inyección de prostaglandina F2 alfa (PGF2α) en el folículo preovulatorio de la yegua

  • Agustina Grippo Laboratorio de Producción Equina, Facultad de Agronomía y Veterinaria, Universidad Nacional de Río Cuarto, Córdoba, Argentina.
  • Javier Aguilar Laboratorio de Producción Equina, Facultad de Agronomía y Veterinaria, Universidad Nacional de Río Cuarto, Córdoba, Argentina.
  • Juan Cuervo-Arango Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
  • Rebeca Martínez-Boví Departamento de Medicina y Cirugía Animal, Facultad de Veterinaria, Universidad Cardenal Herrera, CEU Universities, Alfara del Patriarca, España.
  • Catalina Castañeira Laboratorio de Producción Equina, Facultad de Agronomía y Veterinaria, Universidad Nacional de Río Cuarto, Córdoba, Argentina.
  • Carolina Alonso Laboratorio de Producción Equina, Facultad de Agronomía y Veterinaria, Universidad Nacional de Rio Cuarto, Argentina.
  • Horacio Mouguelar Departamento de Anatomía Animal. Facultad de Agronomía y Veterinaria. Universidad Nacional de Río Cuarto, Córdoba, Argentina.
  • Ana Paula Flores Bragulat Laboratorio de Producción Equina, Facultad de Agronomía y Veterinaria, Universidad Nacional de Río Cuarto, Córdoba, Argentina.
  • Luis Losinno Laboratorio de Producción Equina, Facultad de Agronomía y Veterinaria, Universidad Nacional de Rio Cuarto, Argentina.

Resumen

Las prostaglandinas (PGE2 y PGF2α) ejercen un rol esencial en el proceso de la ovulación en los mamíferos. El objetivo de este experimento fue determinar si la inyección intrafolicular con prostaglandina F2 alfa (PGF2α) administrada en el período preovulatorio inducía la ovulación normal y formación del cuerpo lúteo, confirmado más tarde con la presencia de una vesícula embrionaria. Se utilizaron 6 yeguas mestizas en dos ciclos estrales cada una, con un diseño crossover. El tracto reproductivo de las yeguas fue ecografiado cada 24 h desde el día 15 del ciclo (Día 0 = día de la ovulación) hasta el momento de la punción folicular (Hora 0). La punción ecoguiada del folículo preovulatorio (diámetro ≥ 35mm y presencia de moderado edema uterino) se realizó a través del flanco, inyectando 750 µg de PGF2α diluido en 0,5 ml de agua estéril (grupo tratado n=6) o placebo (0,5 ml de agua de inyección) (grupo control n=6). Previo a la punción, las yeguas fueron inseminadas con semen fresco. Se obtuvieron imágenes ultrasonográficas cada 12 h del folículo punzado y se tomaron muestras de sangre cada 48 h de la vena yugular para determinar los niveles plasmáticos de progesterona. Cinco de las seis yeguas (83%) del grupo tratado, tuvieron fallas en la ovulación y sólo una de las yeguas ovuló pero no se obtuvo preñez. De acuerdo con estos resultados, la inyección intrafolicular con PGF2α no permitiría la ovulación normal y, contrariamente a lo esperado, induciría la formación de folículos hemorrágicos anovulatorios. Además, se observó un retraso en la elevación de progesterona en la única yegua que ovuló.


 


Injection of prostaglandin F2 alpha (PGF2α) into the mare’s preovulatory follicle



Abstract. Prostaglandins (PGE2 and PGF2α) play an essential role in the ovulation process in mammals. The objective of this experiment was to determine whether intrafolicular injection with prostaglandin F2 alpha (PGF2α) administered in the pre-ovulation period induced normal ovulation and corpus luteum formation, it was later confirmed with the presence of an embryonic vesicle. Six mixed-breed mares were used in two estrous cycles each, with a crossover design. The ultrasonographic examination of the reproductive tract was performed every 24 hours from day 15 of the cycle (Day 0 = day of ovulation) until the time of follicular puncture (Hour 0). The ultrasound guided puncture of the preovulatory follicle (diameter ≥ 35 mm and presence of moderate uterine edema) was performed through the flank, injecting 750 µg of PGF2α diluted in 0.5 ml of sterile water (treated group n = 6) or placebo (0.5 ml of injection water) (control group n = 6). Prior to puncture, the mares were inseminated with fresh semen. Ultrasound images were obtained every 12 h of the punctured follicle and blood samples were taken every 48 h from the jugular vein to determine plasma progesterone levels. Five of the six mares (83%) of the treated group had ovulation failures and only one of the mares ovulated but no pregnancy was obtained. According to these results, intrafolicular injection with PGF2α at the concentration used would not allow normal ovulation and contrary to expectations would induce the formation of anovulatory hemorrhagic follicles. In addition, a delay in progesterone rise was observed in the only mare that ovulated.

Citas

Adams, J., Liu, Z., Ren, Y. A., Wun, W. S., Zhou, W., Kenigsberg, S., Librach, C., Valdes, C., Gibbons, W., Richards, J. (2016). Enhanced inflammatory transcriptome in the granulosa cells of women with polycystic ovarian syndrome. The Journal of Clinical Endocrinology & Metabolism. 101 (9): 3459-3468.

Aguilar, J., Castañeira, C., Alonso, C., Flores, A., Marín, J., Cuervo-Arango, J., Martinez-Boví, R., Mougelar, H., Losinno, L. (2018). Intrafollicular injection of prostaglandins in the preovulatory follicle of the mare. Journal of Equine Veterinary Science. 66: 183.

Aguilar, J., Cuervo-Arango, J., Losinno, L. (2015). Folículos Hemorrágicos Anovulatorios en la yegua. Nuevos conceptos sobre un viejo problema en clínica reproductiva. Biotecnologías Reproductivas en Equinos I. FAVE Eds (ISBN 978-987-45862-1-6). 173-187.

Conti, M., Hsieh, M., Park, J. Y., Su, Y. Q. (2006). Role of the epidermal growth factor network in ovarian follicles. Molecular Endocrinology. 20 (4): 715-723.
Couse, J. F., Yates, M. M., Deroo, B. J., Korach, K. S. (2005). Estrogen receptor-β is critical to granulosa cell differentiation and the ovulatory response to gonadotropins. Endocrinology. 146 (8): 3247-3262.

Cuervo-Arango, J. & Domingo-Ortiz, R. (2011). Systemic treatment with high dose of flunixin-meglumine is able to block ovulation in mares by inducing hemorrhage and luteinisation of follicles. Theriogenology. 75: 707–714.

Cuervo-Arango, J. & Newcombe, J.R. (2010). Risk factors for the development of haemorrhagic anovulatory follicles in the mare. Reproduction in Domestic Animals. 45: 473-480.

Cuervo-Arango, J. & Newcombe, J.R. (2012). Ultrasound characteristics of experimentally induced luteinized unruptured follicles (LUF) and naturally occurring hemorrhagic anovulatory follicles (HAF) in the mare. Theriogenology. 77: 514-524.

Daels, P. F. & Hughes, J. P. (1993). The normal estrous cycle. In McKinnon, A. O. and Voss J. L., editors: Equine Reproduction, 1st Edition. Philadelphia: Lea and Febiger. 121-132.

Edelman, A.B, Jensen, J.T., Doom, C., Hannebold, J.D. (2013). Impact of the prostaglandin synthase-2 inhibitor celecoxib on ovulation and luteal events in women. Contraception. 87: 352 – 357.

Gastal, E. L. (2011). Ultrasonographic morphologic of the preovulatory follicle. In Mckinnon, A. O.; Squires E. L.; Vaala, W. E.; Varner,D. D., editors: Equine Reproduction, 2nd Edition. United Kingdom: Wiley-Blackwell. 2032-2054.

Gaytán, F., Tarradas, E., Bellido, C., Morales, C., Sánchez-Criado, J. E. (2002). Prostaglandin E1 inhibits abnormal follicle rupture and restores ovulation in indomethacin-treated rats. Biology of Reproduction. 67 (4):1140-1147.

Gérard, N. & Robin, E. (2019). Cellular and molecular mechanisms of the preovulatory follicle differenciation and ovulation: What do we know in the mare relative to other species. Theriogenology. 160: 163-179.

Ginther, O. J., Gastal, E. L., Gastal, M. O., Beg, M. A. (2008). Dynamics of the equine preovulatory follicle and periovulatory hormones: what’s new? Journal of Equine Veterinary Science. 28 (8): 454-460.

Ginther, O.J., Beg, M.A., Gastal, E.L., Gastal, M.O., Cooper, D.A. (2009). Treatment with human chorionic gonadotropin (hCG) for ovulation induction is associated with an immediate 17β-decrease and a more rapid LH increase in mares. Animal Reproduction Science. 114: 311-317.

Ginther, O.J., Gastal, E.L., Gastal, M.O., Beg, M.A. (2007). Incidence, endocrinology, vascularity, and morphology of hemorrhagic anovulatory follicles in mares. Journal of Equine Veterinary Science. 27: 130-139.

Hsieh, M., Lee, D., Panigone, S., Horner, K., Chen, R., Theologis, A., Lee, D.C., Threadgill, D.W., Conti, M. (2007). Luteinizing hormone-dependent activation of the epidermal growth factor network is essential for ovulation. Molecular and cellular biology. 27 (5): 1914-1924.

Kim, J., Bagchi, I. C., Bagchi, M. K. (2009). Control of ovulation in mice by progesterone receptor-regulated gene networks. Molecular human reproduction. 15 (12): 821-828.

Larentis, G.R., Bastos, H.B.A., Camozzato, G.C., Santos, G.O., Mattos, R.C. (2018). Do therapeutic doses of phenilbutazone affect ovulation process in mare. Journal of Equine Veterinary Science. 66: 150-151.

Lefranc, A. C. & Allen, W. R. (2003). Incidence and morphology of anovulatory haemorrhagic follicles in the mare. Pferdeheilkunde. 19 (6): 611-612.

Li, Q., Jimenez-Krassel, F., Kobayashi, Y., Ireland, J.J., Smith, G.W. (2006). Effect of intrafollicular indomethacin injection on gonadotropin surge-induced expression of select extracellular matrix degrading enzymes and their inhibitors in bovine preovulatory follicles. Reproduction.131: 533-544.

Lim, H., Paria, B. C., Das, S. K., Dinchuk, J. E., Langenbach, R., Trzaskos, J. M., Dey, S. K. (1997). Multiple female reproductive failures in cyclooxygenase 2–deficient mice. Cell. 91 (2): 197-208.

Martínez-Boví, R. & Cuervo-Arango, J. (2016). Follicle Diameter and Systemic Hormone Interrelationships during Induction of Follicle Collapse with Intrafollicular Prostaglandin E2 and F2α in Mares. Reproduction in Domestic Animals. 51: 322–329

Martínez-Boví, R. & Cuervo-Arango, J. (2016). Intrafollicular treatment with prostaglandins PGE2 and PGF2α inhibits the formation of luteinized unrupture follicles and restores normal ovulation in mares treated with flunixin-meglumine. Equine Veterinary Journal. 48: 211 – 217

McCue, P. M. & Squires, E. L. (2002). Persistent anovulatory follicles in the mare. Theriogenology. 58 (2-4): 541-543.

Murdoch, W. J., Hansen, T.R., McPherson, L.A. (1993). A Review - Role of ecosanoids in vertebrate ovulation. Prostaglandins. 46: 85-115

Niringiyumukiza, J. D., Cai, H., Xiang, W. (2018). Prostaglandin E2 involvement in mammalian female fertility: ovulation, fertilization, embryo development and early implantation. Reproductive Biology and Endocrinology. 16: 43.

Paredes, P., Jiménez, C., Hernández, A. (2013). Corpus luteum diameter and serum progesterone level, during the estrous cycle in colombian criollo mares. Revista MVZ Córdoba. 18 (3): 3829-3835.

Peluffo, M.C., Stanley, J., Braeuer, N., Rotgeri, A., Fritzemeier, K.H., Fuhrmann, U., Buchmann B., Adevai, T., Murphy, M.J., Zelinski, M.B., Lindenthal, B., Hennebold, J.D., Stouffer, R.L. (2014). A prostaglandin E2 receptor antagonist prevents pregnancies during a preclinical contraceptive trial with female macaques. Human Reproduction. 29 (7): 1400 –1412.

Pérez, R. S., Jiménez L.M., Gómez Danés A.A.,  Casiano Ventura M. A.,  Quero Carrillo A.R., Pérez Rodríguez, P. (2016). Piroxicam and ovarian changes in adult goat. Nova Scientia. 8: 91-105.
Richards, J. S. (2018). Ovulation. Elsevier. 92-98

Robker, R.L., Russell, D.L., Yoshioka, S., Sharma, S.C., Lydon, J.P., O’Malley, B.W., Espey, L.L., Richards, J.S. (2000). Ovulation: a multi-gene, multistep process. Steroids. 65: 559-570.
Sirois, J & Doré, M. (1997). The Late Induction of Prostaglandin G/H Synthase-2 in Equine Preovulatory Follicles Supports Its Role as a Determinant of the Ovulatory Process. Endocrinology. 138: 4427-34.

Song, J.H, Curry, T.E., Brannstorm, M., LeMaire, W.J., Koods, R.D., Papkoff, H., Janson, P.O. (1987). Inhibition of follicle-stimulating hormone-induced ovulation by indomethacin in the perfused rat ovary. Biology Reproduction. 36: 536-42.

Townson, D. H. & Ginther, O. J. (1987). Duration and pattern of follicular evacuation during ovulation in the mare. Animal Reproduction Science. 15 (1-2): 131-138.

Townson, D. H., Pierson, R. A., Ginther, O. J. (1989). Characterization of plasma progesterone concentrations for two distinct luteal morphologies in mares. Theriogenology. 32 (2): 197-204.
Publicado
2020-07-29
##submission.howToCite##
GRIPPO, Agustina et al. Inyección de prostaglandina F2 alfa (PGF2α) en el folículo preovulatorio de la yegua. Ab Intus, [S.l.], v. 3, n. 5, p. 8-18, july 2020. ISSN 2618-2734. Disponible en: <http://www.ayv.unrc.edu.ar/ojs/index.php/Ab_Intus/article/view/126>. Fecha de acceso: 28 sep. 2020
Sección
Artículos