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Hormones have an important role in regulating fetal metabolism in relation to the prevailing nutritional conditions both in late gestation and during the prepartum period as the fetus prepares for birth. In particular, the pancreatic, thyroid and adrenal hormones all affect fetal uptake and utilization of nutrients for oxidative metabolism, tissue accretion and fuel storage. These hormones also influence the fetal metabolic preparations for the nutritional transition from intra- to extra-uterine life. This review discusses the role of insulin, glucagon, thyroxine, tri-iodothyronine, cortisol and the catecholamines in these processes during normal intrauterine conditions and in response to maternal undernutrition with particular emphasis on the sheep fetus. It also considers the metabolic interactions between these hormones and their role in the maturation of key tissues, such as the liver, skeletal muscle and adipose tissue, in readiness for their new metabolic functions after birth. Endocrine regulation of fetal metabolism is shown to be multifactorial and dynamic with a central role in optimizing metabolic fitness for survival both in utero and at birth., (Copyright © 2021. Published by Elsevier Inc.)

Glucocorticoids (GCs) are important environmental and maturational signals during intrauterine development. Toward term, the maturational rise in fetal glucocorticoid receptor concentrations decreases fetal growth and induces differentiation of key tissues essential for neonatal survival. When cortisol levels rise earlier in gestation as a result of suboptimal conditions for fetal growth, the switch from tissue accretion to differentiation is initiated prematurely, which alters the phenotype that develops from the genotype inherited at conception. Although this improves the chances of survival should delivery occur, it also has functional consequences for the offspring long after birth. Glucocorticoids are, therefore, also programming signals that permanently alter tissue structure and function during intrauterine development to optimize offspring fitness. However, if the postnatal environmental conditions differ from those signaled in utero, the phenotypical outcome of early-life glucocorticoid receptor overexposure may become maladaptive and lead to physiological dysfunction in the adult. This review focuses on the role of GCs in developmental programming, primarily in farm species. It examines the factors influencing GC bioavailability in utero and the effects that GCs have on the development of fetal tissues and organ systems, both at term and earlier in gestation. It also discusses the windows of susceptibility to GC overexposure in early life together with the molecular mechanisms and long-term consequences of GC programming with particular emphasis on the cardiovascular, metabolic, and endocrine phenotype of the offspring., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Hormones have an important role in regulating fetal development. They act as environmental signals and integrate tissue growth and differentiation with relation to nutrient availability. While hormones control the developmental fate of resources available to the fetus, the actual supply of nutrients and oxygen to the fetus depends on the placenta. However, much less is known about the role of hormones in regulating placental development, even though the placenta has a wide range of hormone receptors and produces hormones itself from early in gestation. The placenta is, therefore, exposed to hormones by autocrine, paracrine and endocrine mechanisms throughout its lifespan. It is known to adapt its phenotype in response to environmental cues and fetal demand signals, particularly when there is a disparity between the fetal genetic drive for growth and the nutrient supply. These adaptive responses help to maintain fetal growth during adverse conditions and are likely to depend, at least in part, on the hormonal milieu. This review examines the endocrine regulation of placental phenotype with particular emphasis on the glucocorticoid hormones. It focuses on the availability of placental hormone receptors and on the effects of hormones on the morphology, transport capacity and endocrine function of the placenta., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The present study tested the hypothesis that overexposure to endogenous glucocorticoids in neonatal life alters the reactivity of the hypothalamic-pituitary-adrenal (HPA) axis in ponies at 1 and 2 yr of age. Newborn foals received saline (0.9% NaCl, n = 8, control) or long-acting adrenocorticotropic hormone (ACTH1-24) (Depot Synacthen 0.125 mg intramuscularly twice daily, n = 9) for 5 d after birth to raise cortisol concentrations 5- to 6-fold. At 1 and 2 yr of age, HPA axis function was assessed by bolus administration of short-acting ACTH1-24 (1 μg/kg intravenous) and insulin (0.5 U/kg intravenous) to induce hypoglycemic on separate days. Arterial blood samples were taken at 5 to 30-min intervals before and after drug administration to measure plasma ACTH and/or cortisol concentrations. There were no differences in the basal plasma ACTH or cortisol concentrations or in the cortisol response to exogenous ACTH1-24 with neonatal treatment or age. At 1 and 2 yr of age, the increment in plasma ACTH but not cortisol at 60 min in response to insulin-induced hypoglycemia was greater in ponies treated neonatally with ACTH than saline (P < 0.05). Neonatal cortisol overexposure induced by neonatal ACTH treatment, therefore, alters functioning of the HPA axis in adult ponies., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Pregnancy is generally a co-operative interaction between mother and fetus in which the evolutionary genetic interests of both benefit from production of healthy offspring. While this view is largely supported by empirical data, Kinship Theory predicts that mother and fetus will disagree over the optimum level of maternal investment that maximises their respective fitnesses. This conflict will be more evident with polyandrous than monogamous mating systems, when resources are scarce and in late gestation when the fetus is growing maximally, particularly if conceptus mass is large relative to maternal mass. As the site of nutrient transfer, the placenta is pivotal in the tug-of-war between mother and fetus over resource allocation. It responds to both fetal signals of nutrient demand and maternal signals of nutrient availability and, by adapting its phenotype, regulates the distribution of available resources. These adaptations involve changes in placental size, morphology, transport characteristics, metabolism and hormone bioavailability. They are mediated by key growth regulatory, endocrine and nutrient supply genes responsive to mismatches between nutrient availability and the fetal genetic drive for growth. Indeed, evolution of genomic imprinting and placental secretion of hormones are believed to have been driven by maternal-fetal conflict over resource allocation. Although many of the specific mechanisms involved still have to be identified, the placenta confers optimal fitness on the offspring for its developmental environment by balancing conflict and cooperation in the allocation of resources through generation of nutrient transport phenotypes specific to the prevailing nutritional conditions and/or fetal genotype., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The placenta evolved to support development of the fetus, and so potentially plays a key role in the aetiology of developmental programming through its impact on nutrient transfer. Placental transport efficiency depends on a variety of parameters, including surface area for exchange, thickness of the interhaemal membrane and density of transporter proteins inserted into the trophoblast membranes. Here, we review recent studies that tested whether adaptations of placental efficiency are induced in the mouse placenta when maternal nutrient supply and fetal demand are manipulated experimentally. Naturally small placentas, and those exposed to maternal undernutrition, displayed structural changes indicative of accelerated maturation at E16, with enlargement of the labyrinth exchange zone at the expense of the endocrine junctional zone. These changes were associated with increased transport of a non-metabolisable amino acid analogue per gram of placenta, and expression of genes encoding specific System A transporters. Up-regulation of transporters was also observed when a mismatch between placental size and fetal demand was generated through genetic manipulation of the Igf2/H19 axis. Conversely, overgrowth of the placenta induced by deletion of H19 resulted in reduced transport capacity and expression of transporter genes. We conclude that under conditions when the maternal nutrient supply or placental size may be limiting for normal fetal growth, the placenta adapts so as to increase its transport capacity. Hence, it ameliorates the effects of environmental cues that would otherwise lead to more extensive developmental programming. The P0 transcript of Igf2 appears to be a strong candidate as a mediator of these adaptations in the mouse., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

During late gestation in the mare, rapid fetal growth is accompanied by considerable placental growth and further invasion of the endometrium by microvilli. This growth requires extensive remodeling of the extracellular matrix (ECM). In early pregnancy, we know that matrix metalloproteinase (MMP)-9 and -2 are involved in the endometrial invasion during endometrial cup formation. The present study investigated whether MMPs are found in fetal fluids later in gestation and during parturition, and if there was a difference in their activities between normal and preterm delivery. Amniotic fluids were collected from pony mares during the latter half of gestation, and amniotic and allantoic fluids from pony and thoroughbred mares at foaling. The fluids were analysed for the activity of MMP-9 and -2, and TIMPs using zymography techniques. There was an increase (P = 0.002) in activity of latent MMP-9 when approaching normal foaling, and a decrease (P < 0.001) during foaling. MMP-2 activity did not change through gestation, or during foaling. When comparing samples from pregnancies resulting in preterm deliveries with samples from foaling mares, the activity of MMP-9 was lower (P < 0.001) and MMP-2 activity was higher (P = 0.004) during foaling than preceding preterm delivery. The activity of MMP-9 was lower (P = 0.002) prior to preterm delivery than before delivery of a live foal at term, whereas no difference (P = 0.07) was demonstrated for latent MMP-2 activity when comparing the same groups. The activity of TIMP-2 was higher (P < 0.001) in the pre-parturient period before normal foaling than preceding preterm delivery. These results suggest that MMPs may have a role as markers for high risk pregnancy in the mare., (Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Low birth weight is associated with an increased incidence of adult glucose intolerance, type 2 diabetes and cardiovascular disease in humans. In pregnant rats, dietary calorie or protein deprivation results in growth retarded pups, which become glucose intolerant adults with abnormal hepatic glucose metabolism and gluconeogenic enzyme activities. However, whether these abnormalities are present before birth remain unknown., Methods and Results: This study examined the effects of manipulating dietary protein and carbohydrate intake during rat pregnancy on the fetal and maternal hepatic activities of the gluconeogenic enzymes, glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK). Wistar rats were fed ad libitum with either standard chow throughout pregnancy (25% protein, 57% carbohydrate, n=6) or an isocaloric, low protein, high carbohydrate diet (LPHC, 8% protein, 81% carbohydrate) for different periods of pregnancy (early, 0-10 days, n=6; late, 10-20 days, n=7; throughout, 0-20 days, n=6) before tissue collection at day 20. The LPHC diet had no effect on fetal or placental weights, or on fetal hepatic activities of G6Pase and PEPCK in the early LPHC group. In contrast, fetuses of dams fed the LPHC diet in late or throughout pregnancy had lower body and placental weights, and higher hepatic G6Pase and PEPCK activities than controls. Maternal hepatic G6Pase activity was elevated in all LPHC groups, while maternal PEPCK activity was only increased significantly in the late LPHC group., Conclusions: Feeding a LPHC diet, particularly during late pregnancy, therefore, up-regulates fetal and maternal hepatic glucogenic capacity.

Objective: To determine the effects of 2 maternal injections with dexamethasone on the calculated oxygen and glucose deliveries to fetal cerebral and peripheral circulations during acute hypoxemia in sheep., Study Design: Beginning at 124 days, ewes received 2 intramuscular injections of either dexamethasone (2 x 12 mg, n = 10) or saline solution (2 x 2 mL, n = 12) 24 hours apart. Hypoxemia (1 hour) was induced 32 hours after the first injection (H1) and 3 days after the second (H2)., Results: In saline solution-treated fetuses, glucose delivery was unchanged or increased in femoral and carotid circulations, respectively, during H1 and H2. In dexamethasone-treated fetuses, the increase in glucose delivery to the head tended to be greater during H1 and was significantly enhanced in dexamethasone- vs saline solution-treated fetuses during H2., Conclusion: Two maternal injections with dexamethasone significantly enhanced glucose delivery to the head during acute hypoxemia in the ovine fetus.

In humans, low birth weight is associated with an increased risk of metabolic dysfunction in adult life. Many of these metabolic disorders have an endocrine origin and are accompanied by abnormal hormone concentrations. This has led to the hypothesis that adult metabolic disease arises in utero as a result of programming of key endocrine systems during suboptimal intrauterine conditions associated with fetal growth retardation. This review examines the experimental evidence for prenatal endocrine programming with particular emphasis on endocrine axes involved in growth and metabolism, namely, the hypothalamic-pituitary-adrenal axis, the endocrine pancreas and the somatotrophic axis. It also considers how changes in these endocrine systems contribute to the programming of metabolism in later life.

The facilitative glucose transporters 1 and 3 are the major routes for glucose transport across placental membranes. Using light and electron microscope immunocytochemistry on acrylic sections this study shows a similar pattern of expression from mid to late pregnancy in all four ruminants examined [cow, deer, ewe and goat]. GT1 and GT3 are localised on different membrane layers of the synepitheliochorial placental barrier and glucose must utilise both isoforms sequentially to pass from the maternal to fetal circulations. It is suggested that this arrangement is designed to support the high glucose utilisation by the multilayered placenta in the ruminant.

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.

Objective: The purpose of the study was to test the hypotheses that maternal treatment with dexamethasone leads to a reduction in basal umbilical blood flow and diminishes the fetal umbilical hemodynamic response to acute hypoxemic stress in sheep., Study Design: While under general anesthesia, 23 ewes and their fetuses were instrumented with vascular catheters and transonic blood flow probes around a uterine and umbilical artery at 117 days of gestation (term, approximately 145 days). At 124 days, the ewes were injected intramuscularly with 2 doses of either dexamethasone (12 mg) or saline solution at 24-hour intervals. All animals experienced 2 episodes of hypoxemia during treatment (125+/-1 days) and after treatment (128+/-1 days)., Results: Maternal dexamethasone treatment caused a sustained increase in fetal arterial blood pressure (from 41+/-3 mm Hg to 45+/-3 mm Hg) and a transient fall in umbilical vascular conductance (from 6.2+/-0.9 mL. min(-1). [mm Hg](-1) to 5.4+/-0.7 mL. min(-1). [mm Hg](-1)). During both episodes of hypoxemia, there was a significant increase in umbilical blood flow in the controls, but not in the dexamethasone-treated animals., Conclusion: Maternal dexamethasone treatment with doses used in human clinical practice significantly decreased basal umbilical vascular conductance and prevented the normal increase in umbilical blood flow that is induced by acute hypoxemia in fetal sheep.

Objectives: The effect of dexamethasone on tissue angiotensin-converting enzyme (ACE) was investigated in fetal sheep., Study Design: Pulmonary and renal ACE concentrations were measured in 16 sheep fetuses at between 127 and 131 days of gestation (term 145+/-2 days): 6 were untreated, whereas 10 were chronically catheterized and infused intravenously with either saline solution (0.9%, n=4) or dexamethasone (45-60 microg. kg(-1). d(-1), n=6) for the previous 2 days. The dexamethasone dose increased plasma dexamethasone to around one fifth of that measured in newborn human infants delivered after maternal dexamethasone treatment., Results: Over the period of infusion, arterial blood pressure increased significantly in the dexamethasone (+6.8+/-1.5 mm Hg, P<.05) but not saline-treated fetuses (+1.6+/-0.6 mm Hg). At delivery, pulmonary ACE in the dexamethasone-infused fetuses (1.24+/-0.26 nmoles hippurate. min(-1). mg protein(-1)) was significantly greater than in the control fetuses (0.50+/-0.07 nmoles. min(-1). mg protein(-1), P<.005); renal ACE was unchanged by dexamethasone treatment. Overall, pulmonary ACE and blood pressure were correlated on the last day of infusion (r=0.70, P<.05)., Conclusion: The rise in pulmonary ACE seen in dexamethasone-treated sheep fetuses may contribute, in part, to the glucocorticoid-induced increase in blood pressure.

The insulin-like growth factors, IGF-I and IGF-II, have an important role in fetoplacental growth throughout gestation. They have metabolic, mitogenic and differentiative actions in a wide range of fetal tissues including the placenta. Both Igf1and Igf2genes are expressed in fetal tissues. Expression of the Igf2gene is more abundant than Igf1 gene expression during mid to late gestation. Both IGF's are also present in the fetal circulations with 3-10 fold higher levels of IGF-II than IGF-1 during late gestation. Expression of the Igfgenes is developmentally regulated in a tissue specific manner and can be affected by nutritional and endocrine conditions in utero. Deletion of either Igfgene of the Igf1rgene retards fetal growth while over-expression of IGF-II leads to fetal overgrowth. In mice, placental growth is affected only by manipulation of the Igf2gene. The IGF's also effect the growth of individual fetal tissues and influence the uptake and utilization of nutrients by the fetal and placental tissues. Circulating concentrations and tissue expression of the IGF's are reduced by undernutrition and deficiency of nutritionally sensitive hormones, such as insulin, thyroxine and glucocorticoids. In general, the Igf1gene is more responsive to these stimuli than the Igf2gene. In addition, the effects of the IGFs on feto-placental growth can be amplified or attenuated by the IGF binding proteins, which are themselves regulated by nutritional and endocrine signals. The Igf2gene appears to provide the constitutive drive for intrauterine growth via its placental effects and direct paracrine actions on fetal tissue while the Igf1gene regulates fetal growth in relation to the nutrient supply.

Adverse intrauterine conditions occurring during early to mid-gestation or throughout the whole of gestation influence placental weight and the distribution of placentome types in sheep. However, no study to date has investigated the effect of a reversible period of adverse intrauterine conditions during late gestation upon fetal and placental weight and placentome distribution in sheep. Twenty-two sheep fetuses were chronically instrumented with an inflatable cord occluder, amniotic and vascular catheters and with a Transonic flow probe around an umbilical artery. At 125 days (term isca.145 days) the occluder was inflated to reduce umbilical blood flow by ca.30 per cent for 3d in 12 fetuses (umbilical cord compressed, UCC). The occluder was then deflated and umbilical blood flow allowed to return to baseline. The remaining 10 fetuses acted as sham-operated controls in which the occluder remained deflated at all times. At 135-137dGA ewes were humanely killed and tissues collected, weighed and placentomes classified. A reduction in umbilical blood flow by approximately 30 per cent from baseline for 3 days in UCC fetuses led to mild fetal asphyxia throughout the period of cord-compression. After deflation of the occluder cuff, umbilical blood flow returned to a level that was significantly greater than that measured during baseline. Umbilical cord compression had no effect on fetal body weight but significantly increased fetal adrenal weight relative to body weight. While the total number of placentomes was not altered by cord-compression, total placentome weight and the total weight of C/D-type placentomes were both reduced in UCC relative to control placentae. In addition, the mean weight of placentomes, and of C/D-type placentomes specifically, was significantly lower in UCC relative to control placentae. When expressed as a percentage of the total number of placentomes in the placenta, there was a significantly lower percentage of C/D-type placentomes in UCC relative to control placentae. In addition, there was a significant relationship between the total number of placentomes and the percentage C/D-type placentomes in control, but not UCC, placentae. The data suggest that a temporary, reversible period of adverse intrauterine conditions occurring late in gestation in sheep has persisting effects upon the placenta, mean placentome weight and placentome distribution.

Large granulated binucleate cells (BNCs) producing placental lactogen (PL) and pregnancy-associated glycoproteins (PAG) are present in all ruminant placentae throughout pregnancy. These BNC account for 15-20% of the cells in ovine trophectoderm for most of gestation but decrease in number close to term at the same time that fetal cortisol levels rise. The present study investigated the effects of cortisol on the BNC population using immunohistochemistry to count BNCs in ovine placentomes during late gestation and after experimental manipulation of the fetal cortisol level by fetal adrenalectomy and exogenous cortisol infusion. Abolition of the prepartum rise in fetal cortisol prevented the normal decline in BNC numbers towards term. Conversely, raising cortisol levels in immature fetuses to prepartum values prematurely reduced placental BNC numbers. However, a small population of BNC remained, even at the highest cortisol concentrations. When all the data were combined irrespective of treatment or gestational age, there was a significant inverse correlation between fetal plasma cortisol and the number of BNCs in the ovine placenta. These findings show that cortisol regulates the BNC population in ovine placenta during late gestation. They also have important implications for the production of PL and PAG during ovine pregnancy.

Objective: To characterize propofol anaesthesia in pregnant ponies., Animals: Fourteen pony mares, at 256 ± 49 days gestation, undergoing abdominal surgery to implant fetal and maternal vascular catheters., Materials and Methods: Pre-anaesthetic medication with intravenous (IV) acepromazine (20 µg kg -1 ), butorphanol (20 µg kg -1 ) and detomidine (10 µg kg -1 ) was given 30 minutes before induction of anaesthesia with detomidine (10 µg kg -1 ) and ketamine (2 mg kg -1 ) IV Maternal arterial blood pressure was recorded (facial artery) throughout anaesthesia. Arterial blood gas values and plasma concentrations of glucose, lactate, cortisol and propofol were measured at 20-minute intervals. Anaesthesia was maintained with propofol infused initially at 200 µg kg -1 minute -1 , and at 130-180 µg kg -1 minute -1 after 60 minutes, ventilation was controlled with oxygen and nitrous oxide to maintain PaCO 2 between 5.0 and 6.0 kPa (37.6 and 45.1 mm Hg) and PaO 2 between 13.3 and 20.0 kPa (100 and 150.4 mm Hg). During anaesthesia flunixin (1 mg kg -1 ), procaine penicillin (6 IU) and butorphanol 80 µg kg -1 were given. Lactated Ringer's solution was infused at 10 mL kg -1 hour -1 . Simultaneous fetal and maternal blood samples were withdrawn at 85-95 minutes. Recovery from anaesthesia was assisted., Results: Arterial blood gas values remained within intended limits. Plasma propofol levels stabilized after 20 minutes (range 3.5-9.1 µg kg -1 ); disposition estimates were clearance 6.13 ± 1.51 L minute -1 (mean ± SD) and volume of distribution 117.1 ± 38.9 L (mean ± SD). Plasma cortisol increased from 193 ± 43 nmol L -1 before anaesthesia to 421 ± 96 nmol L -1 60 minutes after anaesthesia. Surgical conditions were excellent. Fetal umbilical venous pH, PO 2 and PCO 2 were 7.35 ± 0.04, 6.5 ± 0.5 kPa (49 ± 4 mm Hg) and 6.9 ± 0.5 kPa (52 ± 4 mm Hg); fetal arterial pH, PO 2 and PCO 2 were 7.29 ± 0.06, 3.3 ± 0.8 kPa (25 ± 6 mm Hg) and 8.7 ± 0.9 kPa (65 ± 7 mm Hg), respectively. Recovery to standing occurred at 46 ± 17 minutes, and was generally smooth. Ponies regained normal behaviour patterns immediately., Conclusions and Clinical Relevance: Propofol anaesthesia was smooth with satisfactory cardiovascular function in both mare and fetus; we believe this to be a suitable anaesthetic technique for pregnant ponies., (Copyright © 2001 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Equine chorionic gonadotropin (eCG) production by the fetally derived endometrial cups appears to be necessary for the establishment and maintenance of normal equine pregnancy. Starting at about the 27th day of pregnancy, an equatorial band of trophectodermal cells on the surface of the spherical conceptus forms the chorionic girdle. This girdle consists initially of flat trophectodermal epithelium which corrugates into folds as the cells proliferate. The folds are then pressed against the uterine epithelium by expansion of the conceptus. The cells on the apices of the folds become binucleate before they start to invade the endometrium at days 35-37. Ultrastructural immunogold labelling shows that they begin to synthesize eCG as early as day 32, before they migrate into and through the maternal epithelium. Clusters of the girdle binucleate cells penetrate deep into the endometrium. The mature cup cell has a cytoplasm full of mitochondria, rough endoplasmic reticulum cisternae, a large Golgi apparatus and a strong immunoreactivity for the glucose transporter 1 isoform on its plasmalemma. Immunocytochemistry also demonstrates that eCG is localized in the Golgi cisternae, and in small dense granules similar to those found in the migrating girdle cell and present both in the Golgi region and at the peripheral plasmalemma. Release of eCG would therefore seem to be by the usual exocytotic mechanism as found for other protein hormones. The small size and absence of any significant accumulation of eCG-containing granules are in marked contrast to the numerous large luteinizing hormone (eLH) containing granules in the equine pituitary gonadotroph, although both hormones, eLH and eCG, show complete identity at the amino acid sequence level. These morphological indicators suggest that the cup cell secretes eCG constitutively (that is, continuously), with no requirement for secretagogues, whereas in the pituitary cell the regulated pathway is utilized capable of massive secretion under appropriate stimulation., (Copyright 2001 Harcourt Publishers Ltd.)

Objective To characterize intravenous anaesthesia with detomidine, ketamine and guaiphenesin in pregnant ponies. Animals Twelve pony mares, at 260-320 days gestation undergoing abdominal surgery to implant fetal and maternal vascular catheters. Materials and methods Pre-anaesthetic medication with intravenous (IV) acepromazine (30 µg kg -1 ), butorphanol (20 µg kg -1 ) and detomidine (10 µg kg -1 ) preceded induction of anaesthesia with detomidine (10 µg kg -1 ) and ketamine (2 mg kg -1 ) IV Maternal arterial blood pressure was measured directly throughout anaesthesia and arterial blood samples were taken at 20-minute intervals for measurement of blood gases and plasma concentrations of cortisol, glucose and lactate. Anaesthesia was maintained with an IV infusion of detomidine (0.04 mg mL -1 ), ketamine (4 mg mL -1 ) and guaiphenesin (100 mg mL -1 ) (DKG) for 140 minutes. Oxygen was supplied by intermittent positive pressure ventilation (IPPV) adjusted to maintain PaCO 2 between 5.0 and 6.0 kPa (38 and 45 mm Hg), while PaO 2 was kept close to 20.0 kPa (150 mm Hg) by adding nitrous oxide. Simultaneous fetal and maternal blood samples were withdrawn at 90 minutes. Recovery quality was assessed. Results DKG was infused at 0.67 ± 0.17 mL kg -1 hour -1 for 1 hour then reduced, reaching 0.28 ± 0.14 mL kg -1 hour -1 at 140 minutes. Arterial blood gas values and pH remained within intended limits. During anaesthesia there was no change in heart rate, but arterial blood pressure decreased by 10%. Plasma glucose and lactate increased (10-fold and 2-fold, respectively) and cortisol decreased by 50% during anaesthesia. Fetal umbilical venous pH, PO 2 and PCO 2 were 7.34 ± 0.06, 5.8 ± 0.9 kPa (44 ± 7 mm Hg) and 6.7 ± 0.8 kPa (50 ± 6 mm Hg); and fetal arterial pH, PO 2 and PCO 2 were 7.29 ± 0.06, 4.0 ± 0.7 kPa (30 ± 5 mm Hg) and 7.8 ± 1.7 kPa (59 ± 13 mm Hg), respectively. Surgical conditions were good but four ponies required a single additional dose of ketamine. Ponies took 60 ± 28 minutes to stand and recovery was good. Conclusions and clinical relevance Anaesthesia produced with DKG was smooth while cardiovascular function in mare and fetus was well preserved. This indicates that DKG infusion is suitable for maintenance of anaesthesia in pregnant equidae., (Copyright © 2001 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

The placenta is the only channel for transport of nutrients to the conceptus and the fetal nutrient demands increase exponentially to term. The 9 kDa calcium binding protein (calbindin, 9CBP) and the iron binding protein uteroferrin (UF) are proving to be reliable markers for epithelia that mediate active transcellular calcium and iron transport and the glucose transporter proteins (GT1 and GT3) for glucose transport by facilitated diffusion. Light and electron microscope immunocytochemistry have been used on perfusion fixed resin embedded material to establish the distribution of 9CBP, UF, GT1 and GT3 in the equine placenta from 100 days of pregnancy to term (336 days). The equine placenta has two main structural components, flat areolae and microcotyledons. From 100 days of pregnancy to term immunoreactive 9CBP is found only in the cytoplasm of the maternal glands and the areolar trophoblast cells with none in the microcotyledons; whereas GT1 is present exclusively in the microcotyledons on the basolateral plasmalemma of both trophoblast and uterine epithelia with GT3 on the apical microvilli. The glands show neither GT1 nor GT3 expression. The areas of both areolae and microcotyledons increase enormously during gestation but there is no indication of increasing amounts of 9CBP, GT1 or GT3 protein per cell. Glucose transport through the placental cell cytoplasm is by diffusion of the free molecule, but calcium ions in transit must be sequestered in some way since the high calcium fluxes needed to support fetal bone growth in later pregnancy would be deleterious to calcium based homeostasis and cellular control systems. Electron microscope immunocytochemistry shows that 9CBP is uniformly distributed in the cytoplasm and nucleoplasm of the areolar trophoblast cells but excluded from all membrane bounded compartments such as mitochondria, Golgi saccules and pinocytotic transport vesicles. Such apical transport vesicles can be identified immunocytochemically by their content of uteroferrin, a component of the secretion from the uterine glands. It is suggested that transcellular calcium transport is therefore based on facilitated diffusion, not the vesicular method followed by the iron in the UF molecules, with 9CBP providing both transfer and sequestration functions for the transient calcium ions. These results show that the equine placenta has transport systems with restricted regional distribution similar to those recently shown for the ruminant placenta., (Copyright 2000 Harcourt Publishers Ltd.)

Scanning electron microscopy was used to examine the microstructure of the maternal and fetal placenta from 25 pregnant ponies (Equus caballus) throughout the second half of gestation. Samples of placenta, 2-6 cm(2)in area, were collected from the antimesometrial region of the pregnant horn at 105 days (n=1), 165-219 days (n=5), 260 days (n=3), 270-277 days (n=3), 313-337 days (n=11) and immediately after spontaneous delivery at term (n=2). The maternal microcaruncle appears to be created from a clustering of about 16 uterine crypts encapsulated in a connective tissue sheath. There is a gestational increase in the depth of the microcaruncle during the second half of pregnancy. The fetal microcotyledon appears to be formed by a clustering of individual fetal villi. The length and branching of the villi increased considerably during the last 2-3 months of gestation. Tufts of from three to six branches were seen arising from close to the base of a villous stem. Branching of the villous stem occurred not only at the base but also along the secondary and tertiary branches. There was evidence of continued branching at the tips of the villi in the few days before birth., (Copyright 2000 Harcourt Publishers Ltd.)

An in vitro incubation technique was used to examine release of lipids from the equine placenta. Placental tissue was obtained at term (n = 5, term = 320-365 days) and earlier in gestation (n = 8, mean = 266 days). Term placentae were incubated at two temperatures, 4 degrees C (control) and 37 degrees C for 2 h. Pre-term placentae were incubated at 37 degrees C with two different concentrations of fatty acid in the medium. Tissues and media were analysed for their lipid concentrations. Term and pre-term placentae released free fatty acid (FFA) and phospholipid into the incubation medium during incubation at 37 degrees C. Long chain polyunsaturated fatty acids derived from the essential fatty acids were released into the media. The fatty acid profiles of the lipids released during incubation more closely resembled those of fetal plasma than maternal plasma lipids as measured in previous studies. These data are consistent with the view that the equine placenta is a source of both FFA and phospholipid for the fetus and that the placenta may provide long chain polyunsaturated fatty acids for the fetal foal.

Disturbances in fetal insulin secretion are associated with abnormalities in fetal growth in a variety of species: excessive insulin secretion can lead to fetal macrosomia while fetal hypoinsulinaemia invariably causes fetal growth retardation. Fetal insulin deficiency caused by pancreatectomy (PX) of the sheep fetus leads to reduced body weight, crown-rump length and limb lengths at delivery near term. The growth rate in utero fell by 40-50% after PX and could be restored to normal values by insulin replacement treatment. These changes in growth were accompanied by reductions of 30-40% in the rates of umbilical uptake, utilization and oxidation of glucose by the sheep fetus. Insulin is therefore a physiological regulator of fetal growth and acts in part by stimulating the cellular uptake of glucose and its preferential use for oxidative metabolism in the fetal tissues.

Objective: The purpose of this study was to determine the roles of fetal plasma glucose and prostaglandin E in controlling fetal breathing movements., Study Design: Five late pregnant ewes with catheterized twin fetuses were fasted for 48 hours; one fetus was kept normoglycemic (by glucose infusion) and the other allowed to become hypoglycemic during this period. Fetal breathing movement and fetal and maternal plasma prostaglandin E and glucose concentrations were measured throughout. Data were analyzed by paired and unpaired t tests., Results: The mean incidence of fetal breathing movement was significantly greater in the normoglycemic fetuses that in the hypoglycemic twins at the end of the fast (p less than 0.05), whereas plasma prostaglandin E levels increased significantly (p less than 0.05) and to the same extent in both groups of fetuses., Conclusion: The reduced incidence of ovine fetal breathing movement that occurs during maternal fasting appears to be primarily caused by fetal hypoglycemia and does not directly involve changes in fetal plasma prostaglandin E.