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The British Equine Veterinary Association (BEVA) was established in 1961 and launched the Equine Veterinary Journal (EVJ) in 1968. This review outlines some of the major advances in equine science and practice that have occurred in that time and the role played by the Journal in facilitating those developments., (© 2011 EVJ Ltd.)

Progesterone (P4), pregnenolone (P5) and their metabolites are present in maternal plasma in pregnant mares. It is believed that one of these progestagens may maintain myometrial quiescence. The aims of this study were to identify specific progestagens in pregnant mares' plasma and determine whether these differed between mares with healthy or compromised pregnancies. Jugular blood samples were collected between 243 and 351 days gestation from 19 healthy Thoroughbred mares and 14 mares with placental pathology, including placentitis, and other clinical problems (uterine torsion/rupture, colic, laminitis). Ten progestagens were identified using gas chromatography-mass spectrometry, of which seven increased significantly with gestational age in healthy mares while P4 was undetectable. Mares with placentitis had increased concentrations of either P5 and/or P4 and several metabolites (5alpha-DHP, P5betabeta, betabeta-diol, betaalpha-diol, 20alpha-5P) suggesting increased fetal production of P5 and/or P4 and increased metabolism in the utero-placental tissues in response to chronic stress. Mares with other placental pathology had raised P4 concentrations while 5alpha-DHP and 3beta-5P were low possibly due to reduced placental function. In mares with problems unrelated to the placenta, most progestagens were substantially lower than control values. Although progestagen profiles differed between normal and abnormal pregnancies, no clear link was demonstrated between maternal plasma concentrations of P4, 5alpha-DHP or any other progestagen and the maintenance of pregnancy.

Reasons for Performing Study: Intrauterine growth retardation (IUGR) impairs post natal adaptive responses and is associated with increased adrenocortical activity in many species., Objectives: To determine whether a restricted or enhanced intrauterine environment affects neonatal adaptation and adrenocortical function in horses., Methods: Embryos from large (577 kg) Thoroughbred (TB) mares were transferred to smaller (343 kg) pony (P) mares and vice versa, to create a restricted (TB-in-P, n = 11) or enhanced (P-in-TB, n = 8) intrauterine environment. Control groups (TB-in-TB, n = 8; P-in-P, n = 7) were also included., Results: Thirty foals were born live at full term (range 314-348 days) and 4 (3 TB-in-P, 1 P-in-TB) were stillborn between 275 and 335 days. TB-in-P foals were significantly (P<0.05) lighter than TB-in-TB, but heavier than P-in-P foals. TB-in-P foals took longer to first stand and suck and some had fetlock hyperextension and low (<4 g/l) plasma immunoglobulin G concentrations. Other foal groups showed normal behavioural responses. Haematological parameters were normal in all 4 groups of foals. Plasma ACTH levels were high at birth and plasma cortisol concentrations increased after delivery and returned to baseline within 6 h post partum in all but the TB-in-P foals, which had elevated levels until 48 h post partum. Plasma cortisol concentrations increased in all groups following exogenous ACTH administered on Days 1 and 5 postpartum., Conclusions: The TB-in-P foals showed IUGR and impaired post natal adaptive responses with basal hypercortisolaemia., Potential Relevance: Foals born following IUGR may require clinical assistance in the early post natal period, but appear mature with respect to adrenocortical function.

In pregnant mares during late gestation, little, if any, progesterone (P4) is found in the maternal circulation. Hence, quiescence of the equine uterus is believed to be maintained by metabolites of pregnenolone and P4 known as progestagens, which are produced by the uteroplacental tissues. However, little is known about the ontogeny, distribution, or actual rates of uteroplacental progestagen production in pregnant mares and their fetuses during the second half of pregnancy. Therefore, the present study measured the rates of uteroplacental uptake and output of eight specific progestagens in chronically catheterized, pregnant pony mares from 180 days to term. No significant uteroplacental uptake of any of the eight individual progestagens was observed from the uterine circulation. In contrast, significant uteroplacental uptake was observed for five of the eight individual progestagens from the umbilical circulation, and the uptakes increased toward term. The major uteroplacental progestagen outputs were 5 alpha-pregnane-3,20-dione (5 alphaDHP) and 20 alpha-hydroxy-5 alpha-pregnan-3-one (20 alpha 5P). These were released into both the umbilical and uterine circulations at rates that increased toward term. The majority of the total uteroplacental 20 alpha 5P output was distributed into the uterine circulation at all gestational ages studied. In contrast, distribution of the total uteroplacental 5 alphaDHP output switched from preferential delivery into the uterine circulation before 220 days of gestation to release predominantly into the umbilical circulation after 260 days. These findings demonstrate that uteroplacental progestagen production changes during the second half of gestation, which may have important implications for the maintenance of pregnancy and the onset of labor in the mare.

This paper describes the use of a latex agglutination assay to measure serum amyloid A (SAA) in the neonatal foal. The normal range and response to clinical disease was determined. This retrospective study evaluated SAA concentrations over the first 3 days postpartum of 226 Thoroughbred foals judged to be clinically healthy. The normal range for each day was determined; levels were found to be significantly highest on Day 2 (Day 1 vs. Day 2 P<0.0001). The 95th percentile for Days 1-3 was 27.1 mg/l. Clinical records of 133 foals, presented as first or second opinion cases, were evaluated. Foals were divided into 4 groups; septicaemia (S), focal infection (FI), failure of passive transfer (FPT) and noninfectious disease (NI). There was a statistically significant difference (P<0.0001) between SAA concentrations of control foals compared to Groups S and FI. There was no statistically significant difference between controls and Groups FPT and NI. When Group NI was compared to Groups S and FI, there was a statistically significant difference (P<0.0001). The authors suggest that SAA determined by this latex agglutination assay might be a helpful aid in the diagnosis of septicaemia and focal infection in neonatal foals; levels >100 mg/l are highly suggestive of infection in young foals.

Equine lung and kidney organogenesis has not previously been examined with the use of unbiased stereological techniques. The present study examined healthy (control) pony and Thoroughbred lungs and kidneys to establish baseline data of organ development from before birth until maturity at age 3-18 years. Whole left lungs and kidneys were collected from 45 equine postmortem examinations (34 Thoroughbred, 11 pony). Stereological techniques were used to estimate whole kidney, cortex and medulla volume, total glomerular number and volume-weighted mean glomerular volume, lung volume, total terminal bronchiolar duct ending number and total gas exchange surface area. Lungs were demonstrated to be more developed at birth in ponies compared with Thoroughbreds. Thoroughbreds showed continued lung development after birth, a unique micromorphogenic postnatal development. Kidneys were developed equally in ponies and Thoroughbreds. This study has provided data on the baseline development of the equiune lung and kidney which can be used in further studies to examine whether the development of these organs is affected by specific illnesses.

Mean glomerular volume has previously been estimated, using stereological techniques, specifically the point-sampled intercept (PSI), either from isotropic or from vertical sections. As glomeruli are approximately spherical structures, the same stereological technique was carried out on vertical and arbitrary sections to determine whether section orientation had any effect on mean glomerular volume estimation. Equine kidneys from 10 individuals were analysed using the PSI method of estimating volume-weighted mean glomerular volume (MGV); for each kidney, arbitrary and vertical sections were analysed. MGVs were not significantly different between arbitrary and vertical sections (P = 0.691) when analysing the data with the paired t test; when plotting MGV estimates from arbitrary sections against those from vertical sections the intercept was found not to be significantly different from zero (P > 0.8) and the slope of the regression line not to be significantly different from 1.0 (P > 0.4). For the estimation of MGV in equine kidneys using PSI, arbitrary sections may be used if it is not possible to use isotropic or vertical sections, but some caution must be exercised in the interpretation of results so gained.

Progesterone or progestagens are thought to maintain myometrial quiescence in pregnant mares, although this has not been proven. In the present study, the contractility of the equine myometrium was tested in vitro using samples collected from pregnant mares (n=33) between day 68 and day 340 of gestation. Myometrial samples were equilibrated in aerated Krebs buffer and subjected to one or more of these treatments: (i) oxytocin only; (ii) initial oxytocin treatment followed by combined oxytocin and progesterone or another progestagen; and (iii) initial oxytocin treatment followed by Krebs buffer followed by progestagen; (iv) initial progesterone treatment followed by progesterone and oxytocin. Spontaneous contractile activity did not occur within 180 min. The oxytocin-only treatment resulted in a significant (P < 0.01) dose-dependent increase in myometrial resting tension. Myometrial contraction amplitude and frequency tended to increase and decrease, respectively, with increasing concentrations of oxytocin, but the effect was not significant. However, there was no correlation between the amplitude and frequency of myometrial contractions and gestational age. Treatment with progestagens did not alter the amplitude or frequency of oxytocin-stimulated myometrial contractions, regardless of whether progestagens were given with oxytocin (treatment (ii)), without oxytocin (treatment (iii)) or before oxytocin treatment (treatment (iv)). These data support the results of in vivo studies on the stimulatory effect of oxytocin on equine myometrium and indicate that progestagens are ineffective at controlling myometrial contractility in vitro. It is hypothesized that other hormones may be involved in this process.

Progesterone, oestrogen and glucocorticoid receptor concentrations in the uterus and mammary glands of pregnant mares during mid- to late gestation (from day 150 of gestation to term) were measured by binding assays to investigate the hormonal mechanisms involved in pregnancy maintenance and lactation. Uterine progesterone receptor concentrations did not increase significantly with increasing gestational age (from 67.8 +/- 13.7 to 126.1 +/- 48.7fmol mg(-1) protein), whereas oestrogen receptor concentrations were significantly higher in pregnant mares (271.7 +/- 28.9 fmol mg(-1) protein) than in non-pregnant control mares (54.9 +/- 8.1 fmol mg(-1) protein; P < 0.05). There was no correlation between progesterone and oestrogen receptor concentrations, and plasma progesterone and oestrone sulphate concentrations, respectively. In contrast, mammary gland progesterone and oestrogen receptor concentrations decreased significantly with gestational age (from 139.7 +/- 34.6 to 66.7 +/- 22.0 fmol mg(-1) protein and 225.2 +/- 13.3 to 87.6 +/- 14.4 fmol mg(-1) protein, respectively; P < 0.05). The dissociation constant (Kd value) of 16alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione (ORG2058) for progesterone receptors was 22 nmol l(-1). 5alpha-pregnane-3,20-dione (5alpha-DHP) had a high affinity for progesterone receptors, which was similar to that of progesterone, whereas other equine progestagens and 11-[4-(dimethylamino)phenyl]-17-hydroxy-17(1-propynyl)estra-4,9-diene-3-one (RU486) did not bind to progesterone receptors. Oestradiol bound the oestrogen receptors with a Kd value of 0.9 nmol l(-1), which was 10 times more potent than that of 3-hydroxy-1,3,5(10),7-oestratetraen-17-one (equilin). The concentration of glucocorticoid receptors (Kd value = 1.3 nmol l(-1)) was constant between the tissues and reproductive stages. In the present study, striking differences were observed between progesterone receptor expression in the uterus and the mammary glands during pregnancy, probably due to tissue-specific variations in 5alpha-DHP activity. This finding indicates that 5alpha-DHP has an important physiological role in equine gestation.

To enable direct testing of a range of potential toxins or pathogens that might be involved in grass sickness, equine thoracic sympathetic chain ganglion cell lines were established from primary cell cultures by retroviral-mediated transduction of the temperature-sensitive mutant of the establishment oncogene encoding SV40 large T antigen. Morphological and behavioral features, temperature dependence, and immunocytochemical characteristics of the cell lines were investigated. The majority of cells were noradrenergic neurons in which dopamine-beta-hydroxylase, the enzyme that catalyzes norepinephrine synthesis, and neuropeptide Y coexisted. Cells treated with plasma from grass sickness cases that had previously been shown to induce autonomic nervous system damage when injected into normal horses showed significantly decreased mitochondrial function after 1 day. After 3 days exposure most cells showed severe degeneration in contrast to those treated with normal plasma. Liver and lung cell lines were also susceptible to plasma, suggesting that the toxin is not specifically neurotoxic.

The aim of this study was to determine glomerular filtration rate (GFR), effective renal plasma flow (RPF) and filtration fraction (FF) values in Pony foals during the first 10 days post partum in order to assess any age-related changes and the reliability of the single injection inulin/p-aminohippurate (PAH) method. Arterial blood pressure and pulse rate were determined in Pony and Thoroughbred (TB) foals during the first 10 days post partum to establish age-related changes, differences between breeds and possible interrelationships with GFR and RPF. Inulin and PAH were injected intravenously (i.v.) in healthy Pony foals (n = 6) on Days 1, 2, 4, 7 and 10 post partum. Blood samples were collected via the contralateral jugular catheter over a 4 h period. Plasma clearances of inulin and PAH showed that GFR and RPF, respectively, remained relatively constant throughout the post natal period, and were similar to values reported for mature horses. The GFR measurements obtained using the inulin method gave clearance values that were significantly higher (P < 0.01) than those of creatinine clearance performed in a separate group of Pony foals (n = 7). Blood pressure and pulse rates were measured using an electronic sphygmomanometer in TB (n = 6) and Pony foals (n = 7) on Days 1, 2, 3, 4, 7 and 10 postpartum. There were no significant differences in these measurements between the breeds, and both cardiovascular parameters increased during the first 3 days post partum. Values remained unchanged for the rest of the study period. Although measurements of GFR, RPF, blood pressure and pulse rates were not determined in the same animals, blood pressure and pulse rates did not appear to correlate with either GFR or RPF in the Pony foals during the post natal period.

Enhanced adrenocortical activity in the fetus is related to the onset of parturition in many species. The aim of this study was to determine the effect of injection of fetal ACTH on gestational length and fetal viability in the horse. Pony mares (n=23) were studied from 300 days gestation. Seven control mares (Group 1) received three consecutive intrafetal injections of sterile water, while fetuses of a further 16 mares received Depot ACTH1-24. These mares were either allowed to foal spontaneously (Group 2, n=4) or delivery was induced within 3 days of the last fetal injection (Group 3, n=7); 5 mares aborted within 48 h of intrafetal ACTH injection. Maternal plasma progestagen concentrations increased significantly (P<0.05) in Groups 2 and 3 mares following intrafetal ACTH injection, compared with Group 1 mares. All Group 1 mares delivered live foals at a median gestational age of 327 days (interquartile range, 323 334), except one that aborted 16 days after the last fetal injection. Gestational length was significantly (P<0.05) shortened in Group 2 mares (median 314 [312-314]) days compared with controls. Group 1 and Group 2 foals showed normal postnatal adaptive responses and endocrine (plasma cortisol/progestagens) patterns. Group 3 mares delivered live foals at 306 (306-308) days gestation except one that aborted. Their foals were less mature compared with Groups 1 and 2 foals. Eight ACTH-injected fetuses were meconium-stained at delivery, including four that were aborted. Eight mares had thickened placentae, including three that aborted. The data show that both precocious maturation of the equine fetus and a significant reduction in gestational length compared with controls may be achieved in pony mares by intrafetal ACTH injections. This is probably mediated via adrenal regulation of fetal maturation and production of maternal progestagens.

Objective: To determine the effect of diet on energy intake, loss, and metabolism in foals 2 to 7 days old., Animals: 14 pony foals., Procedure: Group-A foals suckled their dams, group-B foals were fed milk replacer, and group-C foals were fed by total parenteral nutrition (TPN). Energy balance studies were performed over 8-hour periods on postpartum days 2, 4, and 7., Results: Mean gross energy (GE) intake of group-A foals increased between days 2 and 7. Approximately 3% of GE was excreted in urine and feces, and energy expenditure remained constant. These foals were in positive energy balance, and mean body weight increased. From day 4 onward, group-B foals consumed more energy than did group-A foals because the milk replacer had a higher energy content than did mares' milk. Mean energy loss in group-B foals was 14% of GE on day 2, but this value decreased subsequently. Energy expenditure in group-B foals was less than that in group-A foals, and energy balance was positive. Group-C foals had the lowest energy intake and expenditure; energy balance was negative on postpartum day 2. These foals also had gastrointestinal tract problems., Conclusions: Mares' milk is highly digestible and is correlated with positive energy balance in neonatal foals. Milk replacer initially is less digestible than mares' milk. In this study, TPN was associated with negative energy balance., Clinical Relevance: The data indicate the advantages of enteral feeding with mares' milk and highlight the clinical and technical difficulties associated with TPN.

Major progress on the endocrinology of the pregnant mare has been possible thanks to the catheterised equine fetal preparation developed by Marian Silver. In particular, these preparations led to the identification of the source of progestagens within the feto-placental unit and provided the impetus for further work on their biosynthesis and biological activities. The biosynthesis of the progestagens involves close interaction between the fetus, the endometrium and the placenta, and gives rise to some fundamental biochemical questions. The biological role of the progestagens is also discussed: these compounds may have progestagenic activities but may also play a role in the onset of parturition.

Metabolic rate, rectal temperature Tr and respiratory quotient (RQ) were determined in 16 sick foals, aged 0-182 h. The foals were categorized into three groups: premature, dysmature or those suffering from neonatal maladjustment syndrome. The mean metabolic rate of the premature foals was 71 watts per unit area of body surface (W m(-2)), significantly lower than that of the other two groups. The overall mean metabolic rate for the sick foals was 82 W m(-2), about 25% below that of healthy foals of similar age. Air temperature (Ta) was 9.5-26.3 degrees C, and several foals shivered despite the provision of additional 'warmth' and insulation. Values of Tr were below 38 degrees C until after 4 h postpartum. Thereafter, Tr averaged 38.1 degrees C but fluctuated widely. The RQ (mean value 0.83) was not correlated with Ta. The lower critical temperature for the sick foals was estimated at 24 degrees C, on average. Methods to prevent excessive heat loss from sick foals are suggested.

15-hydroxy prostaglandin dehydrogenase (PGDH) is the critical enzyme that determines metabolism of primary prostaglandins. Its expression is determined in part by steroid hormones, particularly progesterone, formed from delta(5) steroids through 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity. To assess whether the regulation of PGDH might occur in a paracrine, autocrine or intracrine fashion, we used immunohistochemistry (IHC) to determine the localisation of key steroidogenic enzymes in the equine placenta and compared these patterns to the distribution of immunoreactive (IR-) PGDH. Placental tissue was obtained from pony or Thoroughbred mares at about Days 150, 250-280 and >300 of pregnancy (term 320 to 360 days; n=5-8 each group). IR-PGDH, 3beta-HSD, cholesterol side chain cleavage enzyme (P450(scc)) and 17-hydroxylase/lyase (P450(C17)) were localised using specific antibodies and the avidin-biotin peroxidase technique and visualised using diaminobenzidine as substrate. IR-P450(scc) was present in trophoblast cells, but not in maternal tissues of the microcotyledons. In contrast, at Days 150 and 280, IR-PGDH was present in maternal epithelial and interstitial cells in the microcotyledons, but was not detected in trophoblast epithelium, chorioallantois or endometrial glands. After Day 300, IR-PGDH was present in the maternal epithelium and interstitial cells of the placenta and it was also present in trophoblast cells in some specimens.

The purpose of this study was to measure 3beta-HSD activity in the equine placenta and to assess the effect of fetal and maternal blood plasma progestagens on 3beta-HSD activity was measured in 8 late gestation (collected by caesarian section at 250 to 320 days) and 7 term (collected by caesarian section at 250 to 320 days) and 7 term (collected at birth) equine placentae using a tritium release assay with [3alpha-3H] pregnenolone as substrate. Mean +/- s.d. Km(app) and Vmax for term placentae were in general higher than for late gestation placentae (0.129 +/- 0.217 micromol/l and 23.85 +/- 9.1 nmol/mg/h respectively vs. 0.016 +/- 0.048 micromol/l and 17.36 +/- 20.9 nmol/mg/h) but there was no statistical difference between them. Inhibition studies were performed on 3 term placentae and 3 late gestation ones. Steroid concentrations used for inhibition studies were close to blood plasma concentrations (0.5 to 2 micromol/l). 3beta-hydroxy compounds (5alpha-pregnene-3beta, 20alpha-diol and 3beta-hydroxy-5alpha-pregnan-20-one) showed noncompetitive or mixed inhibition. Mean Ki(app) of 0.7 micromol/l. Inhibition was competitive with 20alpha-hydroxy-5alpha-pregnan-3-one with a mean Ki(app) of 0.1 micromol/l.