Relationship Between Dose of Cloprostenol and Age of Corpus Luteum on the Luteolytic Response of Early Dioestrous Mares : a Fiel
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Reprod Dom Anim doi: 10.1111/j.1439-0531.2011.01940.x ISSN 0936-6768 1 2 Short Communication 3 4 5 Relationship Between Dose of Cloprostenol and Age of Corpus Luteum on the 6 7 2 Luteolytic Response of Early Dioestrous Mares: A Field Study 8 9 J Cuervo-Arango1,2 and JR Newcombe1 10 1Equine Fertility Clinic, Warren House Farm, Barracks Lane, Brownhills, West Midlands, UK; 2Departamento de Medicina y Cirugı´a Animal, 11 Facultad de Veterinaria, Universidad CEU Cardenal Herrera, Moncada, Spain 12 13 14 15 Contents 16 as a single bolus, partial luteolysis is achieved in most 17 The objective of this study was to establish and characterize mares (Troedsson et al. 2001; Nie et al. 2003a,b; Berg- 18 the relationship between the dose of cloprostenol (37.5, 250, felt et al. 2006; Newcombe 2007; Tosi et al. 2008). 3 500 and 750 lg) and the age of the early corpus luteum (CL) 19 Clinically, mares with partial luteolysis undergo a (80, 88, 96, 104 and 112 h) on the luteolytic response of significant decrease in peripheral progesterone concen- 20 mares. Behavioural oestrus and ultrasonographic signs of tration within 24 h of treatment to approximately 21 return to oestrus were considered as the occurrence of full ⁄ 22 1–2 ng ml with a subsequent rebound in progesterone luteolysis. A total of 298 mares were divided into groups concentration (Bergfelt et al. 2006). In addition, the CL 23 according to dose of cloprostenol and CL age. There was an 24 effect of dose of cloprostenol (p < 0.001) and age of the CL decreases in diameter to ultrasonographically undetect- 25 at the time of treatment (p < 0.001) on the percentage able size within 6 days of treatment, and the mare 26 of mares with full luteolysis. The efficacy of 37.5 lgof ovulates without showing oestrous signs (Bergfelt et al. 27 d-cloprostenol was similar to that of 250 lg of d,l-clopros- 2006). 28 tenol (p > 0.05) and that of 500–750 lg (p > 0.05). The Repeated treatments with PGF or cloprostenol in higher dose groups (500 and 750 lg) induced full luteolysis 29 early dioestrus (1–4 days post-ovulation) have been more frequently than the lower dose groups (37.5 and 250 lg) attempted (Mocklin et al. 2006; Holland and Pinto 30 96–104 h post-ovulation. There was no effect of CL age or 2008; Rubio et al. 2008). In the latter studies, most 31 cloprostenol dose on the interovulatory interval (p > 0.05). 32 mares underwent partial luteolysis with resurgence in In conclusion, the effect of cloprostenol on the percentage of progesterone concentration. In addition, protocols 33 mares undergoing full luteolysis is dose-dependent. However, 34 this effect is only evident in mares with CLs aged between 96 involving repeated treatments to control the oestrous 35 and 104 h. There is no advantage of administering more than cycle are not practical in field conditions owing to extra Ò labour costs resultant from increased handling. 36 500 lg of d,l-cloprostenol (Estrumate ), to obtain a higher 37 percentage of mares with full luteolysis in mares with CLs The dose of the luteolytic agent and the age of the 38 aged 80–112 h. CL within the first 4 days of the oestrous cycle are 39 likely to influence the proportion of mares that respond with partial or full luteolysis. However, to date, no 40 Introduction 41 dose-rate study that tests the effect of different doses 42 Prostaglandin F2a (PGF) and its analogues are widely administered to mares at different days in early used in equine practice to shorten the oestrous cycle by dioestrus has been performed. The knowledge of this 43 44 inducing luteolysis. Cloprostenol, amongst other PGF relationship between the dose of the luteolytic agent, 45 analogues, is commonly used in practice. This synthetic the age of the CL and the proportion of mares with full compound is much more potent than the naturally luteolysis is relevant to equine reproduction. There may 46 47 occurring PGF (dinoprost), and whereas the manufac- be clinical indications in which it is needed to bring a turer’s recommended clinical dose is 5 mg for dinoprost recently ovulated mare back in oestrus as soon as 48 Ò (Lutalyse ; Pfizer), it is only 250 lg for cloprostenol possible. 49 Ò 50 (Estrumate ; Scering-Plough Animal Health Ltd). The Over the last few years, data on reproductive clinical 51 recommended dosage is intended for mares with ‘mature outcome of mares treated with different doses of 52 corpora lutea’, i.e., five or more days old. However, it is cloprostenol within the first 4 days after ovulation have known that a much lower dosage (less than a tenth of 53 been collected in our clinic. The objective of this study 54 the recommended dose of PGF) is needed to induce full was to establish and characterize the relationship 55 luteolysis in mares with older corpus luteums (CLs) between the dose of cloprostenol and the age of the (Handler et al. 2004; Barker et al. 2006). It has been early CL on the proportion of mares with full luteolysis. 56 l 57 shown that only 8.75 g of cloprostenol (around 30 This was expressed as the percentage of mares that 58 times less than the recommended dose) was effective in showed behavioural and ultrasonographic signs of inducing full luteolysis in mares known to be in mid to return to oestrus following the luteolytic treatment. It 59 60 late dioestrus (>10 days post-ovulation; Newcombe was hypothesized that both the dose of cloprostenol and 61 et al. 2008). the age of the CL at the time of treatment would have a On the other hand, if PGF or cloprostenol is positive and significant relationship with the proportion 62 £ 63 administered in early dioestrus ( 4 days post-ovulation) of mares undergoing full luteolysis. Ó 2011 Blackwell Verlag GmbH RDA 1940 Dispatch: 28.10.11 Journal: RDA CE: Mary Jennefer A. Journal Name Manuscript No. -B Author Received: No. of pages: 6 PE: Gomathi V 2 J Cuervo-Arango and JR Newcombe 1 Materials and Methods CL is expressed as the oldest possible time (e.g. a CL of 2 Experimental design 80 h, could be 72–80 h old). 3 4 This is a retrospective study involving reproductive data 5 of 298 mares. The data were obtained during the Corpus luteum age groups 6 breeding seasons (March–September) of 2006–2010. According to the age of the CL at the time of treatment, 7 The mares were treated for clinical reasons at different the mares were divided into five different CL-age 8 times relative to the day of ovulation with either: groups. The age groups were the following: 80, 88, 96, 9 1 37.5 lg of d-cloprostenol (0.5 ml sc of Gene- 104 and 112 h post-ovulation. The cut points for the 10 stranÒ; Forte Healthcare Ltd, Naul, Ireland) 80 h youngest and oldest groups were estimated based on 11 (n = 19), 88 h (n = 13), 96 h (n = 23), 104 h preliminary results: mares with CLs younger than 80 h 12 (n = 30) and 112 h (n = 20) post-ovulation. were known to hardly respond with full luteolysis to any 13 2 250 lg of d,l-cloprostenol (1 ml sc of EstrumateÒ; of the luteolytic treatments attempted with different 14 Scering-Plough Animal Health Ltd, Welwyn doses. On the other hand, it was known that most mares 15 Garden City, UK) 80 h (n = 5), 88 h (n = 17), (treated even with small luteolytic doses) responded 16 96 h (n = 13), 104 h (n = 8) and 112 h (n = 4) when the CL age was more than 112 h. 17 post-ovulation. 18 3 500 lg of d,l-cloprostenol (2 ml sc of EstrumateÒ) 19 80 h (n = 18), 88 h (n = 50), 96 h (n = 23), Cloprostenol dose 20 104 h (n = 8) and 112 h (n = 4) post-ovulation. All mares were treated by subcutaneous administration 21 4 750 lg of d,l-cloprostenol (3 ml sc of EstrumateÒ) with one of the four different doses of cloprostenol. The 22 three largest dose groups were 250, 500 and 750 lgof 80 h (n = 5), 88 h (n = 10), 96 h (n = 18), Ò 23 104 h (n = 7) and 112 h (n = 3) post-ovulation. d,l-cloprostenol (250 lg⁄ml of Estrumate , Scering- 24 Plough Animal Health Ltd). Therefore, the final volume 25 The dose of cloprostenol is per mare, regardless of of product of EstrumateÒ was equivalent to 1, 2 and 26 body weight. 3 ml for 250, 500 and 750 lg of d,l-cloprostenol, 27 respectively. The smallest dose group was 37.5 lgofd- Ò 28 Animals cloprostenol, equivalent to 0.5 ml of Genestran 29 (75 lg⁄ml of GenestranÒ; Forte Healthcare Ltd). 30 The data were collected from a total of 298 mares, According to the data sheet information of GenestranÒ, 31 resident to or visiting a veterinary clinic in the UK the recommended dose of d-cloprostenol for mares with 32 (northern hemisphere) during the breeding seasons of a ‘mature CL’ is 22.5–37.5 lg. The reduction in dose 33 2006–2010. Most mares were Irish Draught and crosses compared with the racemic form (d,l-cloprostenol) is 34 between Irish Draught and Thoroughbred, with also based on the higher potency of the active dextrorotatory 35 some Standardbred, Thoroughbred and Warmblood isoform (d-cloprostenol) resultant from the removal of 36 mares.