Proceedings of the 5th International Symposium on EQUINE ...

Havemeyer Foundation Monograph Series No. 3ADMINISTERED OESTROGENS ARE LUTEOLYTICDURING EARLY PREGNANCY IN MAREST. A. E Stout and W. R. Allen*Department <strong>of</strong> Equine Sciences, Utrecht University, Section <strong>of</strong> Reproduction, Yalelaan 12, 3584 CMUtrecht, The Ne<strong>the</strong>rlands; *Equine Fertility Unit, Mertoun Paddocks, Woodditton Road, Newmarket,Suffolk CB8 9BH, UKINTRODUCTIONRecent surveys have reported early pregnancy loss(EPL) rates <strong>of</strong> between 5 and 24% in young,healthy mares and up to 70% in aged, subfertilemares (see Ball 1993 for review), <strong>the</strong>rebyconfirming that EPL is a significant cause <strong>of</strong>economic loss to <strong>the</strong> horsebreeding industry. In <strong>the</strong>present monograph, Carnevale et al. report similarrates <strong>of</strong> EPL for pregnancies established byembryo transfer (12–25%) and <strong>the</strong>y discuss some<strong>of</strong> <strong>the</strong> factors that may have contributed to <strong>the</strong>selosses. In general, while it is clear that <strong>the</strong> majority<strong>of</strong> EPL occurs within <strong>the</strong> first 35 days <strong>of</strong> gestation,when maintenance <strong>of</strong> <strong>the</strong> primary corpus luteum isessential to conceptus survival, <strong>the</strong> conditionsunder which <strong>the</strong> CL might undergo luteolysis in<strong>the</strong> presence <strong>of</strong> a normal conceptus are not wellunderstood. On <strong>the</strong> o<strong>the</strong>r hand, it has been widelyspeculated that oestrogens secreted by <strong>the</strong>developing horse conceptus may effect maternalrecognition <strong>of</strong> pregnancy and luteostasis, as <strong>the</strong>ydo in pigs (Bazer and Thatcher 1977). However,this hypo<strong>the</strong>sis has remained unproven, primarilybecause administration <strong>of</strong> exogenous oestrogensdoes not reliably prolong luteal activity in cyclingmares. Indeed, G<strong>of</strong>f et al. (1993) reported that <strong>the</strong>administration <strong>of</strong> oestrogens to mares in latedioestrus stimulates, ra<strong>the</strong>r than inhibits,luteolysis, <strong>the</strong>reby mirroring <strong>the</strong> situation in <strong>the</strong>domestic ruminants in which oestrogens promoteluteolysis by enhancing endometrial oxytocinreceptor development and, <strong>the</strong>reby, oxytocininducedPGF 2α release (McCracken et al. 1984).Moreover, in cattle, hormonal treatments given toprotect against failure <strong>of</strong> maternal recognition <strong>of</strong>pregnancy and loss <strong>of</strong> <strong>the</strong> primary CL, namely,exogenous progesterone or a mid-dioestrousinjection <strong>of</strong> a GnRH analogue, have been proposedto do so by reducing circulating oestradiolconcentrations and <strong>the</strong>reby weakening <strong>the</strong>luteolytic drive (Mann and Lamming 1995).Similar treatments are being used increasingly inmares in an attempt to minimise early pregnancyloss, despite a lack <strong>of</strong> evidence to support <strong>the</strong>irefficacy. Fur<strong>the</strong>rmore, <strong>the</strong>re is no rationale forsuch treatments unless it can be established thatoestrogens are pro-luteolytic during earlypregnancy in equids; such an effect is bothunproven and contrary to <strong>the</strong> existing dogma. Theaim <strong>of</strong> this study was to determine if administeredoestrogens might be luteolytic during earlypregnancy in <strong>the</strong> mare and, if so, whe<strong>the</strong>r <strong>the</strong>y actby stimulating PGF 2α release directly or byenhancing endometrial oxytocin-sensitivity.MATERIALS AND METHODSOn Days 14 and 22 <strong>of</strong> pregnancy and Day 14 <strong>of</strong> <strong>the</strong>oestrous cycle, Welsh pony mares (n = 3 in each <strong>of</strong>6 groups) were given ei<strong>the</strong>r an iv injection <strong>of</strong> 0.01mg/kg oestradiol-ß alone, or an im injection <strong>of</strong>0.03 mg/kg oestradiol-ß followed 6 h later by an ivinjection <strong>of</strong> 20 iu/500 kg oxytocin. Jugular veinplasma samples were collected at 10 min intervalsfrom 1 h before to 1 h after oestradiol-ß oroxytocin injection and assayed for <strong>the</strong>irconcentrations <strong>of</strong> 13,14-dihydro,15-keto PGF 2α(PGFM). Additional blood samples were collectedtwice daily to monitor post treatment peripheralprogesterone concentrations and pregnancy wasmonitored by palpation and ultrasound scanning <strong>of</strong><strong>the</strong> reproductive tract on alternate days.RESULTSOestradiol benzoate followed by oxytocin, but notoestradiol-ß alone, caused a rapid decline in93