El tratamiento con ácido mefeprónico después del apareamiento, no tiene efecto en los niveles de progesterona ni en la fertilidad de las ovejas durante la temporada no reproductiva

• Metehan Kutlu Necmettin Erbakan University, Faculty of Veterinary Medicine, Department of Obstetrics and Gynecology. Konya, Türkiye
• Neffel Kürşat Akbulut Necmettin Erbakan University, Faculty of Veterinary Medicine, Department of Obstetrics and Gynecology. Konya, Türkiye

DOI: https://doi.org/10.52973/rcfcv-e35561

Palabras clave: Ácido 2-metil-2-fenoxipropiónico, oveja, fertilidad, ácido mefeprónico, progesterona

Resumen

Este estudio tuvo como objetivo evaluar los efectos del tratamiento post–apareamiento con ácido mefeprónico sobre las concentraciones séricas de P4 y los parámetros reproductivos en ovejas Merino en lactancia temprana durante la temporada no reproductiva. Un total de 92 ovejas Merino, entre 40 y 50 días (d) después del parto, fueron tratadas con una esponja intravaginal que contenía 60 mg de acetato de medroxiprogesterona durante 7 d en la temporada no reproductiva. El día que se retiró la esponja (d 7), se administraron 500 UI de eCG mediante inyección. Las ovejas apareadas se dividieron aleatoriamente en dos grupos: un grupo de control y un grupo de tratamiento. En el grupo de tratamiento (MA) (n=28), las ovejas recibieron una inyección intramuscular de 10 mg·kg^-1 de ácido mefeprónico el d 9 después del apareamiento. En el grupo de control (n=27), las ovejas no recibieron ningún tratamiento farmacológico el d 9 después del apareamiento. Los resultados mostraron que no hubo diferencias estadísticamente significativas (P>0,05) entre el grupo de control y el grupo MA en las tasas de gestación (33,3 y 39,2 %), las tasas de mortalidad fetal temprana (22,2 y 18,2 %), las tasas de parto (77,8 y 81,8 %), las tasas de gemelos (0 y 33,4 %) y el número de crias (1,0 y 1,44). La concentración de P4 en el d 11 después del apareamiento en el grupo MA (2,74 ng·mL-1) no fue significativamente diferente de la del grupo de control (3.16 ng·mL^-1) (P>0,05). Se concluye que el tratamiento con ácido mefeprónico después del apareamiento no mejoró los niveles de P4 ni la fertilidad en ovejas Merino en lactancia temprana durante la temporada no reproductiva.

Citas

Kutlu M, Doğan H, Alkan H, Serbester U, Kutlu HR. Post–mating diclofenac vs. carprofen treatment on serum progesterone levels and reproductive outcomes in Hungarian–Merino ewes during the non–breeding season. Reprod. Domest. Anim. [Internet]. 2022; 57(12):1529-1535. doi: https://doi.org/n4vx DOI: https://doi.org/10.1111/rda.14229

Abella DF. Embryo losses in sheep. Int. J. Zoo. Animal Biol. [Internet]. 2023; 6(2):e000464. doi: https://doi.org/n4vz DOI: https://doi.org/10.23880/izab-16000464

Spencer TE, Johnson GA, Bazer FW, Burghardt RC. Implantation mechanisms: insights from the sheep. Reproduction [Internet]. 2004; 128(6):657-668. doi: https://doi.org/ff2nbt DOI: https://doi.org/10.1530/rep.1.00398

Hashem NM, El–Azrak KM, Nour El–Din AN, Taha TA, Salem MH. Effect of GnRH treatment on ovarian activity and reproductive performance of low–prolific Rahmani ewes. Theriogenology [Internet]. 2015; 83(2):192-198. doi: https://doi.org/gtxx2p DOI: https://doi.org/10.1016/j.theriogenology.2014.09.016

Kutlu M, Dinç DA. The effect of double–dose GnRH injections on reproductive performance parameters following short–term progestagen administration in lactated Awassi ewes during the non–breeding season. Trop. Anim. Health. Prod. [Internet]. 2021; 53(2):277. doi: https://doi.org/n4v2 DOI: https://doi.org/10.1007/s11250-021-02735-x

Khan TH, Beck NFG, Khalid M. The effects of GnRH analogue (buserelin) or hCG (chorulon) on day 12 of pregnancy on ovarian function, plasma hormone concentrations, conceptus growth and placentation in ewes and ewe lambs. Anim. Reprod. Sci. [Internet]. 2007; 102:247-257. doi: https://doi.org/bdqg87 DOI: https://doi.org/10.1016/j.anireprosci.2006.11.007

Lashari MH, Tasawar Z. Effect of GnRH (Dalmarelin) given on day 12 post–mating on ovarian function and embryo development in Lohi sheep at southern Punjab, Pakistan. Pak. J. Life Soc. Sci. [Internet]. 2013 [cited 1 Sep. 2024]; 11(2):165-170. Available in: https://n9.cl/b9zlvz

Olfati A, Moghaddam GH. Effects of GnRH agonist (Cinnarelin) on reproductive performance in synchronized Iranian crossbred ewes during the breeding season. Slovak J. Anim. Sci. [Internet]. 2013 [cited 1 Sep. 2024]; 46(1):1-6. Available in: https://n9.cl/9zr1cq

Sirjani MA, Kohram H, Shahir MH. Effects of eCG injection combined with FSH and GnRH treatment on the lambing rate in synchronized Afshari ewes. Small Rumin. Res. [Internet]. 2012; 106:59-63. doi: https://doi.org/f34n95 DOI: https://doi.org/10.1016/j.smallrumres.2012.04.022

Gumen A. Causes and applications for prevention of embryonic loss in dairy cows. Proceedings of the National 5th Herd Health & Management Congress; 2018 Oct. 14-17 Antalya (Türkiye); 2018; 329-330 p.

Ahmadi M, Bekeschus S, Weltmann KD, von Woedtke T, Wende K. Non–steroidal anti–inflammatory drugs: recent advances in the use of synthetic COX-2 inhibitors. RSC Med. Chem. [Internet]. 2022; 13(5):471-496. doi: https://doi.org/n4v3 DOI: https://doi.org/10.1039/D1MD00280E

Erdem H, Guzeloglu A. Effect of meloxicam treatment during early pregnancy in Holstein heifers. Reprod. Domest. Anim. [Internet]. 2010; 45(4):625-628. doi: https://doi.org/cr5pbh

Aké–López R, Segura–Correa JC, Quintal–Franco J. Effect of flunixin meglumine on the corpus luteum and possible prevention of embryonic loss in Pelibuey ewes. Small. Rumin. Res. [Internet]. 2005; 59(1):83-87. doi: https://doi.org/fdbzzx DOI: https://doi.org/10.1016/j.smallrumres.2004.11.008

Tamura K, Ono A, Miyagishima T, Nagao T, Urushidani T. Profiling of gene expression in rat liver and rat primary cultured hepatocytes treated with peroxisome proliferators. J. Toxicol Sci. [Internet]. 2006; 31(5): 471-490. doi: https://doi.org/bf67wt DOI: https://doi.org/10.2131/jts.31.471

Hotta M, Nakata R, Katsukawa M, Hori K, Takahashi S, Inoue H. Carvacrol, a component of thyme oil, activates PPARα and γ and suppresses COX-2 expression. J. Lipid Res. [Internet]. 2010; 51(1):132-139. doi: https://doi.org/bw2233 DOI: https://doi.org/10.1194/jlr.M900255-JLR200

Astakhova AA, Chistyakov DV, Pankevich EV, Sergeeva MG. Regulation of cyclooxygenase 2 expression by agonists of PPAR nuclear receptors in the model of endotoxin tolerance in astrocytes. Biochemistry (Mosc.) [Internet]. 2015; 80(10):1262-1270. doi: https://doi.org/f7t8tj DOI: https://doi.org/10.1134/S0006297915100065

Taniguchi K, Kizuka F, Tamura I, Sugino N. Prostaglandin F2-alpha stimulates cyclooxygenase-2 expression and prostaglandin F2-alpha synthesis through NF–kappaβ activation via reactive oxygen species in the corpus luteum of pseudopregnant rats. Biol. Reprod. [Internet]. 2010; 83(Suppl. 1):124-124. doi: https://doi.org/n4v4 DOI: https://doi.org/10.1093/biolreprod/83.s1.124

Saha P, Talwar P. Identification of PPREs and PPRE associated genes in the human genome: Insights into related kinases and disease implications. Front. Immunol. [Internet]. 2024; 2(15):1457648. doi: https://doi.org/n4v5 DOI: https://doi.org/10.3389/fimmu.2024.1457648

Yamashita S, Rizzo M, Su T–C, Masuda D. Novel selective PPARα modulator pemafibrate for dyslipidemia, nonalcoholic fatty liver disease (NAFLD), and atherosclerosis. Metabolites [Internet]. 2023; 13(5):626. doi: https://doi.org/n4v6 DOI: https://doi.org/10.3390/metabo13050626

Sciorsci RL. Clinical approach to metabolic and reproductive pathologies: 1. In vivo and in vitro activity of mefepronic acid in postpartum dairy cows. Proceedings of the National 5th Herd Health & Management Congress; 2018 Oct. 14-17 Antalya (Turkey); 2018; p.329-330.

Giampietro L, Ammazzalorso A, Amoroso R, De Filippis B. Development of fibrates as important scaffolds in medicinal chemistry. ChemMedChem. [Internet]. 2019; 14(11):1051-1066. doi: https://doi.org/n4v7 DOI: https://doi.org/10.1002/cmdc.201900128

Rizzo A, Gazza C, Mutinati M, Desantis S, Zizza S, D’Onghia G, D’Onghia G, Pantaleo M, Sciorsci RL. Effects of mefepronic acid (2-phenoxy-2-methyl propionic acid) on hepatic metabolism and reproductive parameters in postpartum dairy cows. Endocr. Metab. Immune Disord. Drug Targets. [Internet]. 2014; 14(2):113-122. doi: https://doi.org/n4v8 DOI: https://doi.org/10.2174/1871530314666140223184913

Aparicio–Cecilio A, Bouda J, Salgado–Hernández EG, Núñez–Ochoa L, Castillo–Mata DA, Gutiérrez–Chávez AJ. Effect of 2-methyl-2-phenoxy propionic acid on serum lipid profile and ovarian activity in dairy cows. Czech J. Anim. Sci. [Internet]. 2012 [cited 1 Sep. 2024]; 57:550-556. Available in: https://n9.cl/82gy6 DOI: https://doi.org/10.17221/6412-CJAS

Hayırlı A, Serbester U, Kaynar Ö. Koyun ve Keçilerde Beslenmenin Enerji Dengesi ve Fertilite Üzerine Etkisi [Sheep and Goats nutrition: effects on energetic status and fertility]. Türkiye Klinikleri J. Vet. Sci. Obstet. Gynecol–Special Topics [Internet]. 2016 [cited 1 Sep. 2024]; 2(1):1-8. Turkish. Available in: https://n9.cl/6vovg

Weems CW, Weems YS, Randel RD. Prostaglandins and reproduction in female farm animals. Vet. J. [Internet]. 2006; 171(2):206-228. doi: https://doi.org/fk8bkc DOI: https://doi.org/10.1016/j.tvjl.2004.11.014

Selvi MH. The use of statistics in Veterinary Sciences and the test methods used. Res. Pract. Vet. Anim. Sci. [Internet]. 2024 [cited 1 Sep. 2024]; 1:43-50. doi : https://doi.org/n4v9

Yang J, Chen L, Zhang X, Zhou Y, Zhang D, Huo M, Guan Y. PPARs and female reproduction: evidence from genetically manipulated mice. PPAR Res. [Internet]. 2008; 2008:723243. doi: https://doi.org/cbxts2 DOI: https://doi.org/10.1155/2008/723243

Vitti M, Di Emidio G, Di Carlo M, Carta G, Antonosante A, Artini PG, Cimini A, Tatone C, Benedetti E. Peroxisome proliferator–activated receptors in female reproduction and fertility. PPAR Res. [Internet]. 2016; 2016:4612306. doi: https://doi.org/gjx5sv DOI: https://doi.org/10.1155/2016/4612306

Pohlmeier AM, Phy JL, Watkins P, Boylan M, Spallholz J, Harris KS, Cooper JA. Effect of a low–starch/low–dairy diet on fat oxidation in overweight and obese women with polycystic ovary syndrome. Appl. Physiol. Nutr. Metab. [Internet]. 2014; 39(11):1237-1244. doi: https://doi.org/f6phd8 DOI: https://doi.org/10.1139/apnm-2014-0073

Ngadjui E, Nkeng–Efouet PA, Nguelefack TB, Kamanyi A, Watcho P. High fat diet–induced estrus cycle disruption: effects of Ficus asperifolia. J. Complement Integr. Med. [Internet]. 2015; 12(3):205-215. doi: https://doi.org/n4wb DOI: https://doi.org/10.1515/jcim-2014-0074

Huang TH, Roufogalis BD. Healing the diabetic heart: modulation of cardiometabolic syndrome through peroxisome proliferator activated receptors (PPARs). Curr. Mol. Pharmacol. [Internet]. 2012; 5(2):241-247. doi: https://doi.org/n7ht DOI: https://doi.org/10.2174/1874467211205020241

Tsur A, Orvieto R, Haas J, Kedem A, Machtinger R. Does bariatric surgery improve ovarian stimulation characteristics, oocyte yield, or embryo quality? J. Ovarian Res. [Internet]. 2014; 7(1):116. doi: https://doi.org/n4wc DOI: https://doi.org/10.1186/s13048-014-0116-0

Pusalkar M, Meherji P, Gokral J, Chinnaraj S, Maitra A. CYP11A1 and CYP17 promoter polymorphisms associate with hyperandrogenemia in polycystic ovary syndrome. Fertil. Steril. [Internet]. 2009; 92(2):653-659. doi: https://doi.org/ff3s48 DOI: https://doi.org/10.1016/j.fertnstert.2008.07.016

Collins JS, Beller JP, Burt Solorzano C, Patrie JT, Chang RJ, Marshall JC, McCartney CR. Blunted day–night changes in luteinizing hormone pulse frequency in girls with obesity: the potential role of hyperandrogenemia. J. Clin. Endocrinol. Metab. [Internet]. 2014; 99(8):2887-2896. doi: https://doi.org/n4wd DOI: https://doi.org/10.1210/jc.2013-3258

McGee WK, Bishop CV, Pohl CR, Chang RJ, Marshall JC, Pau FK, Stouffer RL, Cameron JL. Effects of hyperandrogenemia and increased adiposity on reproductive and metabolic parameters in young adult female monkeys. Am. J. Physiol. Endocrinol. Metab. [Internet]. 2014; 306(11):E1292-E1304. doi: https://doi.org/f57n49 DOI: https://doi.org/10.1152/ajpendo.00310.2013

Banu LM, Begum D, Rahman SA, Mollah FH, Ferdousi S, Habibullah M. Correlation of hyperinsulinemia with hyperandrogenemia in primary infertile women with polycystic ovary syndrome. Mymensingh Med. J. 2015; 24(1):127-132. PMID: 25725679.

Belani M, Purohit N, Pillai P, Gupta S, Gupta S. Modulation of steroidogenic pathway in rat granulosa cells with subclinical Cd exposure and insulin resistance: an impact on female fertility. Biomed. Res. Int. [Internet]. 2014; 2014:460251. doi: https://doi.org/gb9krw DOI: https://doi.org/10.1155/2014/460251

Kort DH, Kostolias A, Sullivan C, Lobo RA. Chemerin as a marker of body fat and insulin resistance in women with polycystic ovary syndrome. Gynecol. Endocrinol. [Internet]. 2015; 31(2):152-155. doi: https://doi.org/n4wf DOI: https://doi.org/10.3109/09513590.2014.968547

Mayer SB, Evans WS, Nestler JE. Polycystic ovary syndrome and insulin: our understanding in the past, present and future. Women´s Health. [Internet]. 2015; 11(2):137-149. doi: https://doi.org/n4wg DOI: https://doi.org/10.2217/WHE.14.73

Turan V, Sezer ED, Zeybek B, Sendag F. Infertility and the presence of insulin resistance are associated with increased oxidative stress in young, non–obese Turkish women with polycystic ovary syndrome. J. Pediatr. Adolesc. Gynecol. [Internet]. 2015; 28(2):119-123. doi: https://doi.org/f684cc DOI: https://doi.org/10.1016/j.jpag.2014.05.003

Kutlu M, Dogan H, Aktug E. Mefepronic acid, a PPAR agonist, is inefficient on reproductive performance of ewes in both early and late postpartum period. Large Anim. Rev. [Internet]. 2023 [cited 1 Sep. 2024]; 29(6):255-259. Available in: https://n9.cl/uvdfl

Diskin MG, Murphy JJ, Sreenan JM. Embryo survival in dairy cows managed under pastoral conditions. Anim. Reprod. Sci. [Internet]. 2006; 96:297-311. doi: https://doi.org/bvw7z3 DOI: https://doi.org/10.1016/j.anireprosci.2006.08.008

Alkan H, Erdem H. İneklerde nonsteroid antiinflamatuar ilaçların reprodüktif amaçlı kullanımı [Reproductive use of nonsteroidal antiinflammatory drugs in cows]. Atatürk Üniversitesi Vet. Bil. Derg. [Internet]. 2018; 131:112-120. Turkish. doi: https://doi.org/n4wh DOI: https://doi.org/10.17094/ataunivbd.289219

Shah, BR. Factors leading to early embryonic death. Nep. Vet. J. [Internet]. 2019; 36:118-125. doi: https://doi.org/n4wj DOI: https://doi.org/10.3126/nvj.v36i0.27765

Puspita RD, Rizal DM, Syarif RA, Sari IP. Role of COX-2 for successful embryo implantation process: A mini–review. J. Med. Sci. [Internet]. 2023; 11(F):31-37. doi: https://doi.org/n4wk DOI: https://doi.org/10.3889/oamjms.2023.9123

Rekawiecki R, Kowalik MK, Slonina D, Kotwica J. Regulation of progesterone synthesis and action in bovine corpus luteum. J. Physiol. Pharmacol. [Internet]. 2008; 59(Suppl9):75-89.

Halloran KM, Hoskins EC, Stenhouse C, Moses RM, Dunlap KA, Satterfield MC, Seo H, Johnson GA, Wu G, Bazer FW. Pre–implantation exogenous progesterone and pregnancy in sheep. II. Effects on fetal–placental development and nutrient transporters in late pregnancy. J. Anim. Sci. Biotechnol. [Internet]. 2021; 12(1):46. doi: https://doi.org/kncb DOI: https://doi.org/10.1186/s40104-021-00567-1

Fermin LM, Pain SJ, Gedye KR, Morel PCH, Kenyon PR, Blair HT. Timing of exogenous progesterone administration is critical for embryo development and uterine gene expression in an ovine model of maternal constraint. Reprod. Fertil. Dev. [Internet]. 2018; 30(12):1699-1712. doi: https://doi.org/n4wm DOI: https://doi.org/10.1071/RD17514

Zerani M, Maranesi M, Brecchia G, Gobbetti A, Boiti C, Parillo F. Evidence for a luteotropic role of peroxisome proliferator–activated receptor gamma: expression and in vitro effects on enzymatic and hormonal activities in corpora lutea of pseudopregnant rabbits. Biol. Reprod. [Internet]. 2013; 88(3):62. doi: https://doi.org/n4wn DOI: https://doi.org/10.1095/biolreprod.112.107383

Bogacka I, Bogacki M. The quantitative expression of peroxisome proliferator activated receptor (PPAR) genes in porcine endometrium through the estrous cycle and early pregnancy. J. Physiol. Pharmacol. [Internet]. 2011[cited 1 Sept 2024]; 62(5):559-565. Available in: https://n9.cl/vhds6

Kurzynska A, Bogacki M, Chojnowska K, Bogacka I. Peroxisome proliferator activated receptor ligands affect progesterone and 17β–estradiol secretion by porcine corpus luteum during early pregnancy. J. Physiol. Pharmacol. [Internet]. 2014 [cited 1 Sep 2024]; 65(5):709-717. Available in: https://n9.cl/6yosa

Kang HJ, Hwang SJ, Yoon JA, Jun JH, Lim HJ, Yoon TK, Song H. Activation of peroxisome proliferators–activated receptor δ (PPARδ) promotes blastocyst hatching in mice. Mol. Hum. Reprod. [Internet]. 2011; 17(10):653-660. doi: https://doi.org/b4b6kb DOI: https://doi.org/10.1093/molehr/gar030