Post–Mating Mefepronic acid treatment has no effect on Progesterone levels and fertility in early lactating ewes during the non–breeding season

Keywords: 2-methyl-2-phenoxy propionic acid, ewe, fertility, mefepronic acid, progesterone

Abstract

This study aimed to assess the effects of post–mating treatment with mefepronic acid on serum P4 concentrations and reproductive parameters in early lactating Merino ewes during the non–breeding season. A total of 92 Merino ewes, 40-50 days (d) postpartum, were treated with an intravaginal sponge containing 60 mg of medroxyprogesterone acetate for duration of 7 d during the non–breeding season. On the day the sponge was removed (d 7), an injection of 500 IU eCG was administered. The mated ewes were then randomly divided into two groups: a control group and a treatment group. In the treatment group (MA) (n=28), ewes received an intramuscular injection of 10 mg·kg-1 mefepronic acid on d 9 post–mating. In the control group (n=27), the ewes did not receive any drug treatment on d 9 post–mating. The results showed that there were no statistically significant differences (P>0.05) between the Control Group and MA Group in pregnancy rates (33.3% and 39.2%), early fetal mortality rates (22.2% and 18.2), lambing rates (77.8 and 81.8%), twin rates (0 and 33.4%) and litter sizes (1.0 and 1.44). The P4 concentration on d 11 post–mating in the MA group (2.74 ng·mL-1) was not significantly different from that of the control group (3.16 ng·mL-1) (P>0.05). It is concluded that post–mating mefepronic acid treatment did not improve the P4 and fertility in early lactating Merino ewes during the non–breeding season.

Downloads

Download data is not yet available.

References

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Published
2025-02-20
How to Cite
1.
Kutlu M, Akbulut NK. Post–Mating Mefepronic acid treatment has no effect on Progesterone levels and fertility in early lactating ewes during the non–breeding season. Rev. Cient. FCV-LUZ [Internet]. 2025Feb.20 [cited 2025Aug.1];35(1):6. Available from: https://produccioncientifica.luz.edu.ve/index.php/cientifica/article/view/43573
Section
Veterinary Medicine