Uterine haemodynamics in young and aged pregnant mares measured using Doppler ultrasonography.

REASON FOR PERFORMING STUDY: Aged mares with endometrosis suffer higher rates of pregnancy loss than young mares, due to poor placental development. Reduced uterine blood supply may be one contributory factor. OBJECTIVES: To measure uterine artery (UA) blood flow and other Doppler indices throughout pregnancy and compare placental and foal development in young mares and aged mares. METHODS: Thoroughbred mares were grouped according to age and endometrial biopsy score: 1) 6 young mares (mean age 7.3 years, Category ); 2) 6 aged mares (mean age 18.3 years, Category II). Vascular pathology was nil or mild except in one aged mare with moderate perivasculitis. Both UA were scanned fortnightly throughout pregnancy. Total blood flow volume (BFV, ml/min/kg bwt), peak systolic velocity (PSV, cm/s) and resistance index (RI) were determined by pulsed wave, Doppler ultrasound and UA diameter using B-mode. Mixed-effects regression analyses were used to relate vascular parameters with different predictive variables, whilst accounting for the multiple repeated measurements taken from individual horses through the duration of their pregnancies. RESULTS: PSV, RI and total BFV were best predicted by stage of pregnancy (P < 0.001; r2 > 78%). The UA diameter was also associated with stage of pregnancy (P < 0.001; r2 = 87%) and was significantly greater in the gravid horn (P < 0.001). There was a tendency for lower total BFV in older mares (P < 0.05) and they delivered lighter foals than young mares (P < 0.05). Gross placental morphometry was similar, but microscopic surface density of the microvilli was lower (P < 0.02), in aged than young mares. CONCLUSIONS AND POTENTIAL RELEVANCE: Increased uterine blood flow and decreased vascular resistance reflect fetal growth and development of the placental microcirculation. Older mares have poorer placental microvillus development and lighter foals with reduced UA blood flow. Poor uterine blood flow may be an important contributory factor for pregnancy loss in aged mares.

Endocrine adaptations in the foal over the perinatal period.

In adapting to life ex utero, the foal encounters a number of physiological challenges. It has to assume the nutritional, respiratory and excretory functions of the placenta and activate full regulatory control over its own internal environment for the first time. To achieve this, there must be structural and functional changes to a wide range of tissues including several endocrine glands. In most species, including the horse, these maturational changes begin in late gestation and continue into the first few days of neonatal life. Consequently, during this perinatal period, there are major changes in the sensitivity and/or set point of key endocrine axes, which alter the circulating hormone concentrations in the foal. In turn, these endocrine changes are responsible for many of the other physiological adaptations essential for neonatal survival. The perinatal alterations in the hypothalamic-pituitary-adrenal (HPA) axis are particularly important in these processes, although the sympatho-adrenal medullary axis and endocrine pancreas also have key roles in ensuring homeostasis during the multiple novel stimuli experienced at birth. Abnormalities in the perinatal endocrine profile caused by adverse conditions before or after birth may, therefore, lead to maladaptation or aid survival of the newborn foal depending on the specific circumstances. This review examines the perinatal changes in endocrinology in normal and compromised foals and the role of these endocrine changes in the physiological adaptations to extrauterine life with particular emphasis on the HPA axis, adreno-medullary catecholamines and the endocrine pancreas.

Prostaglandins and the regulation of parturition in mares.

Prostaglandins play an essential role during the perinatal period in the mare. Prostaglandin concentrations are low for the majority of pregnancy due to the regulatory action of progestagens on those enzymes responsible for metabolism of prostaglandins. Towards term, prostaglandin concentrations gradually increase, closely associated with upregulation of the fetal hypothalamo-pituitary-adrenal axis, stimulation of the prostaglandin synthesising enzyme PGHS-2 and changes in the ratio of progestagens and oestrogens. Recent evidence in the mare indicates that proinflammatory cytokines are key mediators of prostaglandin synthesis both at term parturition in healthy mares and at preterm parturition associated with placental infection. Prostaglandin concentrations rise substantially during active labour and decline after birth, associated with delivery of the placenta. During induced labour, prostaglandin concentrations are variable depending on the proximity to spontaneous parturition at term. Once the proinflammatory endocrine cascade is initiated, it is difficult to prevent active labour by administration of drugs that reduce prostaglandin concentrations in peripheral plasma. Further work is needed to establish the inter-relationships between prostaglandin production and other endocrine changes associated with labour at term and preterm in the mare.

Maternal dexamethasone treatment in late gestation induces precocious fetal maturation and delivery in healthy Thoroughbred mares.

REASONS FOR PERFORMING STUDY: The foal requires an active hypothalamo-pituitary-adrenal (HPA) axis for organ maturation and post natal survival. Prenatal administration of synthetic glucocorticoids may provide an effective method for inducing fetal maturation safely in the mare. OBJECTIVES: To determine whether dexamethasone administered to late pregnant mares: 1) will induce fetal maturation and precocious delivery; 2) is safe to use and 3) to identify endocrine responses in the mare and foal. METHODS: Pregnant Thoroughbred mares received either 100 mg dexamethasone i.m. (treated n = 5) or 50 ml saline i.m. (control n = 5) at 315, 316 and 317 days of gestation. Plasma progestagens, cortisol and prostaglandin F(2α) metabolite (PGFM) concentrations were measured before and after treatment. The foals were weighed, the crown-rump length (CRL) measured and an adrenal stimulation test performed on Day 1. RESULTS: Dexamethasone significantly (P<0.01) reduced gestation length in treated mares without apparent adverse effects. Plasma progestagens increased (P<0.05), and cortisol and PGFM (P<0.05) decreased, following dexamethasone treatment compared with control mares. Foals were clinically mature but those from dexamethasone treated mares had reduced (P<0.05) CRL, but not bodyweights, compared with controls. Their cortisol concentrations increased following exogenous adrenocorticotrophic hormone stimulation but 2 foals from dexamethasone treated mares showed evidence of adrenal suppression. CONCLUSIONS: Dexamethasone stimulates precocious fetal maturation and delivery in healthy late pregnant mares. However, fetal HPA activity may be suppressed. POTENTIAL RELEVANCE: Dexamethasone treatment could be used to improve foal viability in mares at risk of preterm delivery. The endocrine effects of such a therapy must be evaluated before clinical intervention with glucocorticoids can be recommended.

An investigation into the suitability of a commercial real-time PCR assay to screen for Taylorella equigenitalis in routine prebreeding equine genital swabs.

REASONS FOR PERFORMING STUDY: Standard bacteriological methods for identifying Taylorella equigenitalis in cervical smears are time consuming. Therefore, a more rapid real-time PCR assay was evaluated for its suitability in screening swabs. OBJECTIVE: To compare the results of a commercially available real-time PCR assay with routine microbiological culture for the identification of T. equigenitalis, the causative organism of contagious equine metritis, in equine genital swab samples, under 'field trial' conditions. MATERIALS AND METHODS: Routine prebreeding genital swabs (n=2072) collected from Thoroughbred mares and stallions during 2009 were examined together with stored T. equigenitalis positive material. Swabs were cultured for T. equigenitalis using standard microbiological techniques. Bacterial lysates were isolated from the swabs and examined for the presence of a 16S DNA fragment of T. equigenitalis, using a commercial multiplex real-time PCR assay system. RESULTS: There was complete concordance between positive and negative results obtained by the 2 methods. Real-time PCR also detected T. equigenitalis DNA from swabs that were negative using standard microbiological culture after 6 months' storage at +4 degrees C but from which T. equigenitalis had been isolated following collection. The sensitivities of real-time PCR and bacterial culture were both 10(-3) (equivalent to 3 colony-forming units). CONCLUSION AND CLINICAL RELEVANCE: Routine bacterial culture of T. equigenitalis requires an incubation period of not less than 7 days before a conclusive negative result can be obtained, whereas bacterial extraction and real-time PCR assay can be completed in less than 6 h. The commercially-available PCR assay tested provided a rapid and reliable method for the identification of T. equigenitalis from equine genital swabs and could be usefully employed for the screening of mares and stallions for preseason Horserace Betting Levy Board (HBLB) Code of Practice and in other situations such as for bloodstock sales screening requirements, overcoming the current delays imposed by bacterial culture requirements. Its use could be quality assured by the existing HBLB biannual testing scheme for designated laboratories.

The Endocrinology of equine parturition.

Delivery of viable young requires co-ordination of fetal maturation with the onset of labour at term. In turn, this depends on a cascade of fetal and maternal endocrine events. The sequence of these events is broadly similar in most mammals but there are differences in placental hormone synthesis and in the timing and magnitude of key prepartum endocrine changes between species. In most farm animals, maternal progesterone (P4) levels decline and oestrogen levels increase in the last 5 - 10 days before delivery in response to activation of the fetal hypothalamicpituitary-adrenal (HPA) axis and increased fetal cortisol concentrations. This cortisol surge is also responsible for fetal maturation and increasing uteroplacental prostaglandin (PG) synthesis. In the mare, there is little, if any, P4 in the maternal plasma during late gestation and both progestagens and oestrogens are produced by a feto-placental unit which uses precursors supplied by the fetus to synthesise a range of C21 and C18 steroids, many of which are unique to the horse. Regulation of uterine quiescence and activation is, therefore, complex in the mare near term. Indeed, total progestagen concentrations rise and total oestrogen levels fall in the mare during the last 20 - 30 days of gestation and only show the changes typical of impending parturition in other species in the last 24 - 48 h before delivery. Fetal cortisol concentrations also rise late in gestation in the horse compared to other species. In common with other species, the prepartum endocrine cascade appears to begin in the fetal horse with activation of the fetal HPA axis but, initially, the primary product of the fetal equine adrenal appears to be pregnenolone (P5) and not cortisol. This leads to increased progestagen production by the uteroplacental tissues, which maintains uterine quiescence in the face of increasing uterine stretch caused by the rapidly growing fetus. Very close to term in association with increasing fetal ACTH levels, the fetal equine adrenals appear to switch to producing cortisol. This late cortisol surge induces a period of rapid fetal maturation and may also contribute to increased uteroplacental oestradiol-17 beta and PG production. The fall in P5 availability may reduce uteroplacental progestagen production and lift the block on myometrial contractility. Finally, increased PG secretion activates myometrial contractions, which stimulate oxytocin release via a neuroendocrine reflex. The endocrine regulation of equine parturition, therefore, involves progestagens, oestrogens, PGs and oxytocin as in other species. However, further studies are required to establish the causes and consequences of the rise and fall in maternal progestagens and the extent to which initiation of equine labour depends on the fetal HPA axis.

Effects of norepinephrine and combined norepinephrine and fenoldopam infusion on systemic hemodynamics and indices of renal function in normotensive neonatal foals.

BACKGROUND: Norepinephrine increases arterial blood pressure but may have adverse effects on renal blood flow. Fenoldopam, a dopamine-1 receptor agonist, increases urine output in normotensive foals. The combination of norepinephrine and fenoldopam may lead to improved renal perfusion compared with an infusion of norepinephrine alone. The combined effects of these drugs have not been reported in the horse. HYPOTHESIS: Norepinephrine will alter the hemodynamic profile of foals without affecting renal function. Addition of fenoldopam will change the renal profile during the infusions without changing the hemodynamic profile. ANIMALS: Five conscious pony foals. METHODS: Each foal received norepinephrine (0.3 microg/kg/min), combined norepinephrine (0.3 microg/kg/min) and fenoldopam (0.04 microg/kg/min), and a control dose of saline in a masked, placebo-controlled study. Heart rate (HR), arterial blood pressure (direct), and cardiac output (lithium dilution) were measured, and systemic vascular resistance (SVR), stroke volume, cardiac index (CI), and stroke volume index were calculated. Urine output, creatinine clearance, and fractional excretion of electrolytes were measured. RESULTS: Norepinephrine and a combined norepinephrine and fenoldopam infusion increased arterial blood pressure, SVR, urine output, and creatinine clearance and decreased HR and CI compared with saline. The combination resulted in higher HR and lower arterial blood pressure than norepinephrine alone. CONCLUSIONS AND CLINICAL IMPORTANCE: Norepinephrine might be useful for hypotensive foals, because in normal foals, this infusion rate increases SVR without negatively affecting renal function (creatinine clearance increased). Fenoldopam does not provide additional benefit to renal function. These findings warrant further investigation.

The effects of maternal health and body condition on the endocrine responses of neonatal foals.

REASONS FOR PERFORMING THE STUDY: Chronic and acute alterations in maternal nutrient intake during pregnancy alter pancreatic and hypothalamo-pituitary-adrenal (HPA) axis function in the offspring, before and after birth. Little is known about these effects. OBJECTIVE: To determine whether maternal nutrient restriction caused by natural infection with Streptococcus equi altered endocrine function in neonatal foals born from mares fed a maintenance or high plane of nutrition throughout pregnancy. METHODS: Ten primiparous mares received either a diet to maintain moderate body condition score (Moderate, n = 5) or a near ad libitum feeding regime to maintain a high body condition score (High, n = 5) throughout pregnancy. All mares inadvertently became infected with Streptococcus equi in mid gestation and lost approximately 10% body mass. RESULTS: Maternal insulin and glucose concentrations decreased (P < 0.05) during, and one month following, the weight loss period. High mares weighed more (P < 0.05) at parturition than Moderate mares; all foals were healthy. Gestational age, foal bodyweights, placental and clinical parameters after birth were no different between the 2 groups. Foal plasma cortisol and glucose responses to exogenous adrenocorticotrophic hormone and insulin, respectively, were similar for both groups. Insulin concentrations during glucose tolerance test were significantly higher (P < 0.05) in foals from Moderate than High mares and compared with foals studied previously from healthy, well-fed mares, suggesting that the beta cell sensitivity to glucose was enhanced in Moderate. CONCLUSION: Acute nutrient restriction in mid gestation caused by maternal illness and inappetence, superimposed on a maintenance feed intake throughout pregnancy, enhanced insulin secretion to glucose in foals. Nutritional programming of pancreatic beta cells, but not the HPA axis, appeared to depend on the level of nutrition before and after the weight loss period. POTENTIAL RELEVANCE: Disturbances in neonatal pancreatic beta cell function programmed during pregnancy may predispose foals to metabolic problems in later life.

Effects of norepinephrine and a combined norepinephrine and dobutamine infusion on systemic hemodynamics and indices of renal function in normotensive neonatal thoroughbred foals.

BACKGROUND: Norepinephrine is a potent vasopressor that increases arterial blood pressure but may have adverse effects on renal blood flow. The combination of norepinephrine and dobutamine may lead to improved renal perfusion compared to an infusion of norepinephrine alone. The effects of these drugs in the normotensive neonatal foal have not been reported. HYPOTHESIS: Norepinephrine increases arterial blood pressure. Adding dobutamine to a norepinephrine infusion will change the renal profile during the infusions without changing the arterial blood pressure. ANIMALS: Eight conscious Thoroughbred foals were used in this study. METHODS: Each foal received norepinephrine (0.1 microg/kg/min), combined norepinephrine (0.1 microg/kg/min) and dobutamine (5 microg/kg/min), and a control dose of saline in a masked, placebo-controlled study. Heart rate, arterial blood pressure (direct), and cardiac output (lithium dilution) were measured, and systemic vascular resistance, stroke volume, cardiac index, and stroke volume index were calculated. Urine output, creatinine clearance, and fractional excretion of sodium, potassium, and chloride were measured. RESULTS: Norepinephrine and a combined norepinephrine and dobutamine infusion increased arterial blood pressure and systemic vascular resistance and decreased heart rate and cardiac index as compared to saline. The combination resulted in higher arterial pressure than norepinephrine alone. There was no significant difference in urine output, creatinine clearance, or fractional excretion of electrolytes with either infusion as compared to saline. CONCLUSIONS AND CLINICAL IMPORTANCE: These data suggest that norepinephrine and a combined norepinephrine and dobutamine infusion cause unique hemodynamic effects without affecting indices of renal function, and this effect warrants further investigation.

Hormone profiles and treatments in the late pregnant mare.

Evaluation of hormone profiles in late pregnancy is one of the major determinants of fetoplacental compromise in equine clinical practice. Use of hormone therapies is subjective and reflects, to a large extent, our lack of understanding about the endocrine relations between the mare, placenta, and fetus. This article describes the normal endocrine events in late gestation, the abnormal hormone patterns associated with fetoplacental dysfunction, and the hormone interventions that are currently used or could be used to improve pregnancy outcome.

Maturation of pancreatic beta-cell function in the fetal horse during late gestation.

At birth, the endocrine pancreas becomes more directly involved in the control of glycaemia than in utero. However, compared with other tissues, relatively little is known about the maturational changes that occur in the fetal endocrine pancreas in preparation for extrauterine life. This study examined the pancreatic beta-cell response to exogenous administration of glucose and arginine in fetal horses with respect to their gestational age and concentration of cortisol, the hormone responsible for prepartum maturation of other fetal tissues. Glucose administration had no effect on fetal insulin secretion between 175 and 230 days of gestation but evoked a rapid insulin response in fetuses closer to term (290-327 days). In late gestation, the beta-cell response was more rapid and greater in magnitude in fetuses with basal cortisol levels higher than 15 ng/ml than in those with lower cortisol values at the time of glucose administration. The fetal beta-cell response to arginine was unaffected by the rise in fetal plasma cortisol towards term. These findings show that there are maturational changes in pancreatic beta-cell function in fetal horses as cortisol levels rise close to term. Primarily, these prepartum maturational changes were in the mechanisms of glucose-stimulated insulin secretion, which would enable the beta cells to regulate glycaemia at the higher glucose levels observed postnatally.

Development of baroreflex and endocrine responses to hypotensive stress in newborn foals and lambs.

OBJECTIVE: The aims of this study were to compare and contrast the development of the cardiac baroreflex and endocrine responses to acute hypotensive stress in healthy newborn pony foals and lambs during the first two weeks of postnatal life. METHODS: Under general anaesthesia, seven Welsh pony foals and six Welsh Mountain lambs were catheterised with hind limb artery and vein catheters. Following post-surgical recovery, at 1 week and 2 weeks of age, blood pressures of the animals were raised and lowered acutely by intravenous infusion of phenylephrine and sodium nitroprusside, respectively. During hypotension, blood samples were taken for measurement of plasma hormones associated with activation of the stress axis. RESULTS: Basal arterial blood pressure increased significantly (P<0.05) between week 1 and week 2 in the absence of any significant change in basal heart rate in foals and with a significant reduction in basal heart rate in lambs. In foals, the slope of the heart rate-blood pressure relationship decreased in response to acute hypertension, and it increased in response to acute hypotension, from week 1 to week 2 (all P<0.05). In contrast, in lambs, the slope of the heart rate-blood pressure relationship decreased with both acute hypertension and acute hypotension from week 1 to week 2 (all P<0.05). In foals, there were significant increases in plasma concentrations of noradrenaline, neuropeptide Y (NPY), vasopressin, adrenocorticotrophic hormone (ACTH) and cortisol in response to hypotension (P<0.05). In lambs, there were also significant increases in plasma concentrations of ACTH and cortisol during hypotension. Plasma concentrations of noradrenaline, NPY and vasopressin were not measured during hypotension in lambs. In foals, although the magnitude of the ACTH response to hypotension was smaller at week 2 than week 1, the increment in plasma cortisol was similar in the two age groups. In contrast, in lambs, the profile of both the ACTH and cortisol responses was similar at week 1 and week 2. CONCLUSION: These data suggest that the increase in basal arterial blood pressure in the foal and the lamb during the first 2 weeks of postnatal life is accompanied by differential maturational changes in the vagal and sympathetic components of the cardiac baroreflex between the two species. These developmental cardiac baroreflex changes occur together with increased adrenocortical responsiveness to acute hypotensive stress, which appears comparatively more mature in lambs than in foals.

Effects of manipulating intrauterine growth on post natal adrenocortical development and other parameters of maturity in neonatal foals.

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.

Peripartal endocrinology in the mare and foetus.

The endocrine profiles in the periparturient mares are dominated by increasing concentrations of progestagens and decreasing oestrogens. These hormones are produced by precursors from the foetus, metabolized by the placenta and act primarily on the maternal uterus. The circulating concentrations of hormones in maternal plasma, generally, represent a small proportion of those metabolized by the foetus and utero-placental tissues. There is clear evidence that the foetal hypothalamo-pituitary-adrenal (HPA) axis initiates the process of foetal maturation and the hormonal cascade which culminates in parturition at term. The endocrine changes associated with abnormal pregnancy and abortion in late pregnancy are less well understood, as are the hormonal treatments needed to avert these problems. Further work is needed to establish the biological role of the various hormones present in pregnant mares and, in particular, those hormones which control myometrial quiescence.

Postnatal insulin secretion and sensitivity after manipulation of fetal growth by embryo transfer in the horse.

This study examined the effects of intrauterine growth on insulin secretion and resistance in newborn foals. Embryo transfer between small pony and large Thoroughbred mares was used to produce four groups of foals with different birth weights (pony in pony n=7; pony in Thoroughbred n=7; Thoroughbred in Thoroughbred n=8; Thoroughbred in pony n=8). On day 2 after birth, glucose (0.5 g/kg) was administered intravenously to the foal and blood samples were taken for 2 h to determine plasma glucose and insulin concentrations. On day 3, insulin sensitivity was assessed by giving insulin (0.75 U/kg i.v.) and measuring the decrement in plasma glucose in the foals. There were no significant differences in insulin secretion, insulin sensitivity or glucose tolerance between the control and growth-retarded Thoroughbred foals. Overgrown pony foals delivered by Thoroughbred mares had higher basal insulin levels and greater beta cell responses to glucose than the other groups of foals. The relationship between plasma glucose and insulin was also significantly steeper in overgrown pony foals than in the other groups. Variations in intrauterine growth rate, therefore, affect postnatal insulin secretion in the horse. More specifically, it is overgrowth, not growth retardation in utero that alters equine beta cell function in the immediate neonatal period.

Ontogeny of uteroplacental progestagen production in pregnant mares during the second half of gestation.

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.

Organogenesis of lung and kidney in Thoroughbreds and ponies.

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.

Effects of maternally administered depot ACTH(1-24) on fetal maturation and the timing of parturition in the mare.

The aims of this study were to ascertain 1) whether fetal maturation could be induced precociously by maternal administration with adrenocorticotrophic hormone (ACTH) and 2) whether maturation could be achieved without significant risk to mare or fetus. Twenty-two mares received either 1 mg (low dose, LD, n = 6) or 4 or 5 mg (higher dose, HD, n = 16) synthetic Depot ACTH(1-24) at 300, 301 and 302 days gestation. Because, during the course of the study, ACTH appeared to have a greater influence on mares mated during the later part of the breeding season, the HD group were divided retrospectively into those mated before (HDE, n = 6), or after (HDL, n = 10), 1st July. All LD mares were mated before 1st July. Control injections were not performed but gestational data were compared retrospectively with 64 untreated, spontaneously foaling pony mares mated between May and October. Plasma progestagen and cortisol concentrations increased significantly (P<0.05) following ACTH administration in all groups, but progestagens were higher and cortisol elevated for longer in HD mares. ACTH stimulated mammary development and milk electrolyte changes in HD mares. Mean +/- s.e. gestation period (days) was significantly (P<0.01) shorter in HDL mares (318 +/- 1.8) compared with LD (335 +/- 3.7), HDE (340 +/- 4.3) and untreated mares mated after 1st July (327 +/- 1.3). All foals were mature except 2 HDL foals which were stillborn. HDL foals had a higher MCV and lower mean bodyweight, indicating they were delivered before full term. In conclusion, maternal ACTH administration appears to accelerate fetal maturation and delivery in pony mares given high doses and mated late in the breeding season. Further work is required to establish the optimal gestational age and dosage for maternal ACTH administration before clinical recommendations can be given for this therapy.

Stereological estimation of volume-weighted mean glomerular volume from arbitrary sections of the equine kidney.

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.