Biomedical subjects

A L Fowden

Publications and source records attributed to A L Fowden.

At least 55 records · Page 3Linked to original sources

PubMed2002

Effects of thyroid hormones on pulmonary and renal angiotensin-converting enzyme concentrations in fetal sheep near term.

In the sheep fetus, pulmonary and renal concentrations of angiotensin-converting enzyme (ACE) increase towards term in parallel with the prepartum surges in plasma cortisol and tri-iodothyronine (T(3)). The ontogenic change in pulmonary ACE has been shown to be induced, at least in part, by cortisol but the role of the thyroid hormones is unknown. Therefore, this study investigated the effects of thyroid hormones on tissue ACE concentration in fetal sheep during late gestation. Pulmonary and renal ACE concentrations were measured in sheep fetuses after experimental manipulation of thyroid hormone status by fetal thyroidectomy and exogenous hormone infusion. In intact fetuses, pulmonary and renal ACE concentrations increased between 127-132 and 142-145 days of gestation (term 145 +/- 2 days), coincident with the prepartum rises in plasma cortisol and T(3). The ontogenic increment in pulmonary ACE concentration was abolished when the prepartum surge in T(3), but not cortisol, was prevented by fetal thyroidectomy. At 143-145 days, ACE concentration in the lungs and kidneys of the thyroidectomised fetuses were both lower than those in the intact fetuses. In intact fetuses at 127-132 days, pulmonary ACE was upregulated by intravenous infusions of either cortisol (2-3 mg/kg per day) or T(3) (8-12 microg/kg per day) for 5 days. Renal ACE was unaffected by cortisol or T(3) infusion. Therefore, thyroid hormones have an important role in the developmental control of pulmonary and renal ACE concentration in the sheep fetus towards term. In addition, the prepartum rise in plasma T(3) appears to mediate, in part, the maturational effect of cortisol on pulmonary ACE concentration.

Animals↗

PubMed2002

Influence of maternal size on placental, fetal and postnatal growth in the horse. I. Development in utero.

The interacting influences of maternal size and fetal genotype on placental and fetal development in the mare were assessed by comparing conventional within-breed Thoroughbred (Tb-in-Tb, n = 7) and Pony (P-in-P, n = 7) control pregnancies established by artificial insemination (AI) with between-breed (Tb-in-P, n = 8; deprived in utero condition and P-in-Tb, n = 7; luxurious in utero condition) experimental pregnancies established by embryo transfer. All foals were born spontaneously and the mean (+/- SEM) duration of gestation in the two groups of control mares was significantly different (P < 0.001) at 325 +/- 3.0 days for the P-in-P pregnancies and 339 +/- 3.0 days for the Tb-in-Tb pregnancies, whereas the durations of gestation for the two experimental groups were very similar and midway between those of the control pregnancies at 332 +/- 2.8 days for the Tb-in-P and 331 +/- 2.7 days for the P-in-Tb. Mean (+/- SEM) foal birth weight and the mean (+/- SEM) values for the mass, gross area and volume of the allantochorion were all highest in the seven Tb-in-Tb pregnancies (53.1 +/- 2.6 kg, 3.8 +/- 0.3 kg, 12.9 +/- 0.3 x 10(3) cm(2), 3.5 +/- 0.2 l, respectively) and lowest in the seven P-in-P control pregnancies (24.0 +/- 1.3 kg, 1.7 +/- 0.1 kg, 8.3 +/- 0.3 x 10(3) cm(2), 1.8 +/- 0.1 l, respectively). These parameters were higher in the seven P-in-Tb pregnancies (37.9 +/- 2.1 kg, 2.7 +/- 0.1 kg, 10.1 +/- 0.5 x 10(3) cm(2), 2.5 +/- 0.1 l, respectively) than in the eight Tb-in-P (33.0 +/- 2.4 kg, 2.3 +/- 0.2 kg, 9.0 +/- 0.5 x 10(3) cm(2), 2.1 +/- 0.1 l) experimental pregnancies. Foal birth weight was positively correlated with the mass (r = 0.84, P < 0.001), gross area (r = 0.87, P < 0.001) and volume (r = 0.91, P < 0.001) of the allantochorion, and maternal weight was also positively correlated with both the mass and gross area of the allantochorion (r = 0.64 and 0.69, respectively; both P < 0.001). Application of stereology to multiple random biopsies recovered from each placenta produced mean values for the surface density of microcotyledons on the allantochorion (S(v)). Values were higher in Thoroughbred than in Pony mares regardless of the breed of fetus being carried. Multiplication of S(v) by the volume of the allantochorion to give the total microscopic area of fetomaternal contact at the placental interface was also positively correlated with foal birth weight (r = 0.84, P < 0.001). Foal birth weight was determined by the microscopic area of fetomaternal contact of the placenta and there were no differences in foal weight per m(2) of placenta regardless of fetal or maternal genomes. Thus, the results indicate that in equids, maternal size interacts with both the maternal and fetal genotypes to control the rate and extent of fetal growth by influencing the gross area of the diffuse allantochorion, and the density, complexity and depth of the microcotyledons on its surface.

Analysis of Variance↗

PubMed2001

Ontogeny of pulmonary and renal angiotensin-converting enzyme in pigs.

The present study investigated the ontogeny of pulmonary and renal angiotensin-converting enzyme (ACE) in foetal and postnatal pigs, and examined the effect of cortisol on tissue ACE in utero. Data were compared with those in sheep at similar ages. Under anaesthesia, tissues and umbilical blood were collected from pig foetuses between 81-115 days of gestation (term, 115+/-2 days). Twelve foetuses delivered at 97+/-2 days were infused with saline or cortisol (3-6 mgkg(-1)day(-1)) using osmotic mini-pumps implanted 6 days previously. Tissues were collected from newborn piglets, and from pigs at 2-4 weeks, 10-12 weeks and 10-12 months of age. Unlike in sheep, gestational age and exogenous cortisol had no effect on pulmonary or renal ACE in pigs. After birth, pulmonary ACE decreased to a nadir at 2-4 weeks and remained low thereafter. Renal ACE increased between 10-12 weeks and 10-12 months. Postnatal changes in tissue ACE may have consequences for cardiovascular, pulmonary and renal function in pigs.

Animals↗

PubMed2001

The sodium channel beta-subunit SCN3b modulates the kinetics of SCN5a and is expressed heterogeneously in sheep heart.

1. Cardiac sodium channels are composed of a pore-forming alpha-subunit, SCN5a, and one or more auxiliary beta-subunits. The aim of this study was to investigate the role of the recently discovered member of the beta-subunit family, SCN3b, in the heart. 2. Northern blot and Western blot studies show that SCN3b is highly expressed in the ventricles and Purkinje fibres but not in atrial tissue. This is in contrast to the uniform expression of SCN1b throughout the heart. 3. Co-expression of SCN3b with the cardiac-specific alpha-subunit SCN5a in Xenopus oocytes resulted in a threefold increase in the level of functional sodium channel expression, similar to that observed when SCN1b was co-expressed with SCN5a. These results suggest that both SCN1b and SCN3b improve the efficiency with which the mature channel is targeted to the plasma membrane. 4. When measured in cell-attached oocyte macropatches, SCN3b caused a significant depolarising shift in the half-voltage of steady-state inactivation compared to SCN5a alone or SCN5a + SCN1b. The half-voltage of steady-state activation was not significantly different between SCN5a alone and SCN5a + SCN3b or SCN5a + SCN1b. 5. The rates of inactivation for SCN5a co-expressed with either subunit were not significantly different from that for SCN5a alone. However, recovery from inactivation at -90 mV was significantly faster for SCN5a + SCN1b compared to SCN5a + SCN3b, and both were significantly faster than SCN5a alone. 6. Thus, SCN1b and SCN3b have distinctive effects on the kinetics of activation and inactivation, which, in combination with the different patterns of expression of SCN3b and SCN1b, could have important consequences for the integrated electrical activity of the intact heart.

Animals↗

PubMed2001

A novel method for controlled and reversible long term compression of the umbilical cord in fetal sheep.

1. In fetal sheep during late gestation the aims of the present study were to (1) develop a technique for inducing prolonged but reversible periods of controlled compression of the umbilical cord and (2) characterise the cardiovascular, endocrine and metabolic responses to this challenge. 2. Under 1-2 % halothane anaesthesia, 16 Welsh Mountain sheep fetuses were chronically instrumented at 118 +/- 2 days of gestation (term is ca 145 days) with an inflatable occluder cuff around the umbilical cord, amniotic and femoral vascular catheters and with transit-time flow probes around the contra-lateral femoral artery and an umbilical artery. At 125 days, umbilical blood flow was reduced by 30 % from a pre-determined 24 h baseline for 3 days by automated servo-controlled inflation of the occluder cuff (n = 8). The occluder was then deflated allowing return of umbilical blood flow to baseline. The remaining eight fetuses were used as sham-operated controls in which the occluder was not inflated throughout the protocol. Fetal cardiovascular variables were recorded at 8 s intervals and arterial blood samples taken for measurement of blood gases, glucose and lactate and plasma adrenaline, noradrenaline and vasopressin concentration throughout the study. 3. Automated servo-controlled inflation of the occluder cuff, programmed to reduce umbilical blood flow by 30 % from baseline, reduced umbilical blood flow by 30.2 +/- 1.7 %, with a coefficient of variation during compression of 6.5 +/- 1.1 %. Sustained partial compression of the umbilical cord produced falls in fetal arterial pH, P(a,O2), percentage O(2) saturation of haemoglobin, and hindlimb oxygen delivery, and increases in P(a,CO2), haemoglobin concentration, arterial blood oxygen carrying capacity and in blood glucose and lactate concentrations. While the reductions in P(a,O2), percentage saturation of haemoglobin and hindlimb oxygen delivery and the increase in P(a,CO2) were sustained throughout compression, the reduction in arterial pH and the increase in arterial oxygen carrying capacity had returned towards baseline values by 48 h compression. Fetal blood lactate concentrations reached a peak at 8 h of compression and, thereafter, were maintained at an elevated level relative to baseline. 4. Partial compression of the umbilical cord produced fetal hypertension, a reduction in femoral blood flow and, consequently, an increase in calculated fetal femoral vascular resistance for the duration of the challenge. In addition, the fall in heart rate measured in sham control fetuses by the end of the study, did not occur in cord-compressed fetuses. Cosinor analysis on 24 h rhythms of cardiovascular data indicated a significant increase in the amplitude of the 24 h rhythm in heart rate in cord-compressed fetuses relative to sham controls during the period of compression or sham-compression. Furthermore, cord compression led to an increase in fetal plasma noradrenaline, but not adrenaline and vasopressin concentrations relative to sham control fetuses. 5. In conclusion, a novel reversible method for controlled, long-term compression of the umbilical cord in sheep has been developed. The data show that sustained, partial compression of the umbilical cord produced moderate but sustained asphyxia, which resolved after the end of the compression period, and induced changes in fetal cardiovascular, endocrine and metabolic functions.

Animals↗

PubMed2001

Intra-uterine programming of the endocrine pancreas.

In altricial species such as the rat and mouse, there is good evidence for the intra-uterine programming of the endocrine pancreas. Changes in the intra-uterine nutritional environment cause alterations in the structure and function of the islets which have life-long effects and predispose the animal to glucose intolerance and diabetes in later life. In rodents, the islets develop relatively late in gestation and undergo substantial remodelling in the period immediately after birth. Hence, the critical window for islet development in these animals is short and readily accessible for experimental manipulation. The short life-span of these species also means that elderly animals can be studied within a reasonable time frame. In precocious species, such as guinea pigs and farm animals, intra-uterine programming of the endocrine pancreas is less well established. In part, this may be due to difficulties in identifying the critical window for development as islet formation and remodelling begin at an earlier stage of gestation and continue for longer after birth. The long life-span of these animals and the relative insulin resistance of adult ruminants compared to other species also make it difficult to establish whether fetal changes in islet development have long-term consequences. In the human, the main phase of islet development occurs during the second trimester, although remodelling occurs throughout late gestation and early childhood. There is, therefore, a relatively long period in which early changes in islet development could be reversed or ameliorated in the human. Although the human epidemiological observations suggest that the fetal origin of adult glucose intolerance is due primarily to changes in insulin sensitivity rather than to defective insulin secretion, subtle changes in islet morphology and function sustained in utero may well contribute to the increased susceptibility to type 2 diabetes observed in adults who were growth-retarded in utero.

Animals↗

PubMed2001

Developmental expression analysis of thyroid hormone receptor isoforms reveals new insights into their essential functions in cardiac and skeletal muscles.

Nuclear thyroid hormone (TH) receptors (TR) play a critical role in mediating the diverse actions of TH in development, differentiation, and metabolism of most tissues, but the role of TR isoforms in muscle development and function is unclear. Therefore, we have undertaken a comprehensive expression analysis of TRalpha 1, TRbeta 1, TRbeta 2 (TH binding), and TRalpha 2 (non-TH binding) in functionally distinct porcine muscles during prenatal and postnatal development. Use of a novel and highly sensitive RNase protection assay revealed striking muscle-specific developmental profiles of all four TR isoform mRNAs in cardiac, longissimus, soleus, rhomboideus, and diaphragm. Distribution of TR isoforms varied markedly between muscles; TRalpha expression was considerably greater than TRbeta and there were significant differences in the ratios TRalpha 1:TRalpha 2, and TRbeta 1:TRbeta 2. Together with immunohistochemistry of myosin heavy chain isoforms and data on myogenesis and maturation of the TH axis, these findings provide new evidence that highlights central roles for 1) TRalpha isoforms in fetal myogenesis, 2) the ratio TRalpha 1:TRalpha 2 in determining cardiac and skeletal muscle phenotype and function; 3) TRbeta in maintaining a basal level of cellular response to TH throughout development and a specific maturational function around birth. These findings suggest that events disrupting normal developmental profiles of TR isoforms may impair optimal function of cardiac and skeletal muscles.

Animals↗

PubMed2001

Plasma adrenocorticotropin and cortisol concentrations during acute hypoxemia after a reversible period of adverse intrauterine conditions in the ovine fetus during late gestation.

The present study determined the pituitary-adrenal responses to acute hypoxemia after a period of reversible adverse intrauterine conditions produced by partial compression of the umbilical cord for 3 days in the sheep fetus during late gestation. At 118 +/- 2 days gestation (term is approximately 145 days), 12 sheep fetuses were instrumented under halothane anesthesia with an occluder cuff around the umbilical cord, amniotic and vascular catheters, and a transit-time flow probe around an umbilical artery. In 6 of the fetuses at 125 days, umbilical blood flow was reduced by about 30% from baseline for 3 days (UCC), after which the occluder was deflated. The remaining 6 fetuses acted as sham-operated controls in which the occluder was not inflated. All fetuses were then subsequently subjected to 2 periods of acute hypoxemia, elicited by reducing the maternal inspired fraction of oxygen (FiO(2)) at 2 +/- 1 and 5 +/- 2 days after the end of cord compression or sham compression. In addition, 4 fetuses from each group were subjected to an ACTH challenge 1-2 days after the final episode of acute hypoxemia. Maternal and fetal arterial blood samples were taken at appropriate intervals during cord compression, acute hypoxemia, and ACTH challenge for analyses of blood gases, pH, and plasma ACTH and cortisol concentrations. Partial compression of the umbilical cord produced reversible mild fetal asphyxia, a transient increase in fetal plasma ACTH, and a progressive increase in fetal plasma cortisol. At 5 +/- 2 days after the end of compression, despite similar blood gas status between the groups, basal plasma cortisol, but not ACTH, concentrations were significantly greater in compressed fetuses relative to sham controls. However, this dissociation did not affect a similar increment in fetal plasma ACTH and cortisol concentrations during acute hypoxemia or in the fetal plasma cortisol response to the ACTH challenge in either group. An increase in adrenocortical mass occurred in fetuses preexposed to partial compression of the umbilical cord relative to sham controls. The data suggest that fetal exposure to a reversible period of adverse intrauterine conditions produced by partial compression of the umbilical cord does not affect the magnitude of the fetal hypothalamic-pituitary-adrenal axis response to subsequent acute hypoxemia, but it leads to resetting of basal hypothalamic-pituitary-adrenal axis function in the fetus. The mechanism for this resetting may include an increase in adrenocortical steroidogenic synthetic capacity, but it is not due to a change in adrenocortical sensitivity to ACTH. Inappropriate fetal glucocorticoid exposure after reversible periods of adverse intrauterine conditions has important implications for fetal and postnatal development.

Acute Disease↗

PubMed2001

Regulation of glucogenesis by thyroid hormones in fetal sheep during late gestation.

The effects of thyroid hormone deficiency in utero on the fetal glucogenic capacity were investigated by measuring glucose production and hepatic levels of glycogen and gluconeogenic enzymes in normal sheep fetuses in the fed and fasted states during late gestation and in those made thyroid hormone deficient by fetal thyroidectomy (TX). In the fed state, fetal TX had no effect on glucose uptake, utilisation or production by the fetus. It also had no apparent effect on the glycogen content or activities of the key gluconeogenic enzymes in the fetal liver. In addition, fetal plasma concentrations of insulin, cortisol, adrenaline or noradrenaline were unaffected by fetal TX in the fed state. In contrast, the rates of fetal O(2) consumption and CO(2) production per kilogram fetal bodyweight were significantly lower in TX than in intact fetuses in the fed state (P<0.05). TX prevented fetal glucose production in response to maternal fasting for 48 h. It also abolished the normal decreases in the fetal glucose carbon oxidation fraction, the rate of CO(2) production from glucose carbon and in the fraction of the umbilical O(2) uptake used for glucose carbon oxidation that occur during fasting in intact fetuses. At the end of the fast, plasma noradrenaline concentrations and hepatic levels of glycogen, glucose 6-phosphatase, fructose diphosphatase and alanine aminotransferase were significantly lower in TX than in intact fetuses. These observations show that thyroid hormones are essential for glucogenesis in the sheep fetus during late gestation and suggest that these hormones act both on the hepatic glucogenic pathways and on the mechanisms activating glucogenesis in utero.

Alanine Transaminase↗

PubMed2000

Ontogenic and nutritionally induced changes in fetal metabolism in the horse.

1. Using the Fick principle and tracer methodology, the metabolic rates of chronically catheterized fetal foals (n = 24) were measured at different gestational ages during the second half of gestation and in response to maternal fasting for 36 h in late gestation (n = 4, term approximately 335 days). 2. Absolute rates of umbilical blood flow, fetal glucose utilization and umbilical uptake of oxygen (O2) and glucose increased from mid-gestation to 300 days and then plateauxed until term. The absolute rate of umbilical lactate uptake was significant after, but not before, 280 days of gestation. Weight specific rates of umbilical uptake and fetal utilization of glucose decreased progressively throughout the second half of gestation. 3. Weight specific rates of CO2 production from glucose carbon were also inversely correlated with gestational age. Umbilical lactate uptake per kilogram of fetus was lower after 320 days than between 281 and 300 days. In contrast, no gestational trends were observed in the weight specific rates of fetal O2 uptake and urea production. Glucose production by the fetal horse was negligible, even very close to term. 4. Maternal fasting for 36 h reduced the rate of umbilical uptake and utilization of glucose production but had no effect on the rates of endogenous glucose production and umbilical uptake of oxygen and lactate by the horse fetus. 5. The observations show that fetal metabolism is highly dependent on glucose in the horse compared to the sheep in mid- and late gestation. Different species therefore adopt different strategies in meeting the nutritional demands of the growing fetus during the second half of gestation.

Animal Nutritional Physiological Phenomena↗

PubMed2000

Role of cortisol in the ontogenic control of pulmonary and renal angiotensin-converting enzyme in fetal sheep near term.

1. This study examined the ontogeny of angiotensin-converting enzyme (ACE) concentration in the lungs and kidneys of fetal, newborn and adult sheep, and investigated the effects of cortisol infusion on tissue and plasma ACE in the chronically catheterised ovine fetus. 2. Pulmonary and renal ACE in utero increased from 113 days of gestation towards term; peak tissue ACE concentrations were observed in fetuses studied at 143 days (term, 145 +/- 2 days). The high level of ACE seen in the fetal lungs close to term was maintained in the lambs and adult ewes whereas renal ACE decreased immediately after birth and rose to a maximal value in the adult ewes. In all groups of animals studied, higher mean concentrations of ACE were observed in the kidneys than in the lungs. Ontogenic increments in pulmonary and renal ACE in utero were coincident with the prepartum cortisol surge. In untreated and saline-infused fetuses, plasma cortisol correlated with both pulmonary (r = 0.83, P < 0.0001) and renal (r = 0.53, P < 0.01) ACE concentrations, irrespective of gestational age. 3. An intravenous infusion of cortisol (2-3 mg kg-1 day-1) at either 113 or 129 days raised plasma cortisol to the level seen near term and caused an increase in pulmonary ACE at both gestational ages. Pulmonary ACE concentration in the cortisol-infused fetuses at 129 days, but not at 113 days, was similar to that observed in the fetuses near term. In contrast, cortisol infusion had no effect on renal ACE concentration at either 113 or 129 days of gestation. Plasma ACE concentration was also increased by exogenous cortisol at 129 days. 4. Therefore, these findings suggest that the ontogenic rise in ACE concentration observed in the lungs of the sheep fetus near term is induced, at least in part, by the prepartum cortisol surge.

Animals↗

PubMed2000

Effect of cortisol on blood pressure and the renin-angiotensin system in fetal sheep during late gestation.

The effects of cortisol on blood pressure and the circulating components of the renin-angiotensin system (RAS) were investigated in sheep fetuses during late gestation and after exogenous cortisol infusion. Plasma cortisol concentration was greater in fetuses at 140 +/- 1 days of gestation (term 145 +/- 2 days) compared to those studied earlier in gestation (128 +/- 1 days), although, because of wide inter-animal variation, no differences were observed in blood pressure or plasma angiotensin II (AII), renin or angiotensinogen (Ao) concentrations. At 129 +/- 1 days of gestation, an infusion of cortisol for 5 days (2-3 mg kg(-1) day(-1) i.v.) increased plasma cortisol concentration to a value normally seen close to term. This rise in plasma cortisol was accompanied by increases in blood pressure and plasma concentrations of AII, renin and Ao. When observations from all fetuses were considered, plasma cortisol concentration correlated with plasma AII and renin, and blood pressure correlated with plasma cortisol and AII concentrations. Intravenous administration of an AII type 1 (AT(1))-specific receptor antagonist (3 mg kg(-1) GR138950) caused a reduction in blood pressure in all fetuses; the hypotensive response was greatest in fetuses studied near term and in the cortisol-treated fetuses. Overall, the magnitude of the hypotension induced by GR138950, and the concomitant rise in plasma renin, both correlated with the plasma cortisol concentration before GR138950 treatment. These findings show that, in the sheep fetus during late gestation, the RAS becomes more important in the maintenance of resting blood pressure when plasma cortisol concentration is elevated, whether endogenously or exogenously.

Angiotensin II↗

PubMed2000

Separate sites and mechanisms for placental transport of calcium, iron and glucose in the equine placenta.

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.

Acid Phosphatase↗

PubMed2000

Blood chemistry, nutrient metabolism, and organ weights in fetal and newborn calves derived from in vitro-produced bovine embryos.

Calves born after in vitro production (IVP) of embryos often show reduced perinatal viability. The present experiment investigated a series of physiological variables in the immediate prenatal and postnatal period of IVP dairy calves. Fetal IVP and control calves (each n = 7) were prepared with vascular catheters at 248+/-1 day gestation (term = 280 days), and blood samples were taken for five days before premature delivery by cesarean section. IVP fetuses compared with controls had significantly elevated arterial hemoglobin and oxygen content (8.41 vs. 7.52% and 5.75 vs. 3.79%, respectively) whereas lactate level was lowered (1.89 vs. 2.26 mM). The umbilical venous-arterial concentration differences in oxygen, lactate, and glucose indicated that IVP fetuses relied more on lactate and less on glucose as oxidative substrates. The fetal glucose tolerance, and the basal and adrenocorticotropin-stimulated cortisol levels were similar between the groups. In the immediate postnatal period, IVP calves showed elevated venous blood pH (7.294 vs. 7.270), hemoglobin (9.06 vs. 8.25%), oxygen contents (6.33 vs. 4. 64%), K(+) levels (4.89 vs. 4.56 mM), and rectal temperature (38.9 vs. 37.4 degrees C), and lowered blood Na(+) (139.9 vs. 141.0 mM), Cl(-) (100.2 vs. 103.1 mM) and glucose levels (2.86 vs. 3.11 mM). There were no differences in body dimensions and organ weights, except that the fore legs and hind legs were slightly longer in the IVP group (76.1 vs. 72.4 cm and 93.4 vs. 88.8 cm, respectively). Although prenatal and neonatal IVP calves differed from control calves in a number of variables, the effects were relatively minor and provide no direct evidence for the hypothesis that IVP calves have an impaired capacity to adapt to life ex utero. In fact, several parameters indicated enhanced rather than retarded maturation of IVP calves when data from premature calves were compared with data from a group of control calves delivered at term.

Animal Nutritional Physiological Phenomena↗

PubMed2000

Control of ovine hepatic growth hormone receptor and insulin-like growth factor I by thyroid hormones in utero.

By use of RNase protection assays, hepatic growth hormone receptor (GHR) and insulin-like growth factor I (IGF-I) mRNA abundances were measured in sheep fetuses after experimental manipulation of fetal plasma thyroid hormone concentrations by fetal thyroidectomy (TX) and exogenous infusion of triiodothyronine (T(3)) and cortisol. TX abolished the normal prepartum rise in hepatic GHR abundance but had little effect on hepatic GHR gene expression at 127-130 days (term 145 +/- 2 days). By contrast, it upregulated basal IGF-I expression in immature fetal liver by increasing both Class 1 and Class 2 transcript abundance but had no further effects on IGF-I gene mRNA levels at 142-145 days. Raising plasma T(3) to prepartum values by exogenous infusion of either T(3) or cortisol into immature intact fetuses prematurely raised hepatic GHR and IGF-I mRNA abundances to values similar to those seen in intact fetuses at 142-145 days. In TX fetuses, cortisol infusion increased hepatic GHR mRNA but not total IGF-I mRNA abundance at 127-130 days. These findings show that thyroid hormones have an important role in the regulation of hepatic GHR and IGF-I gene expression in fetal sheep during late gestation and suggest that T(3) mediates the maturational effects of cortisol on the hepatic somatotropic axis close to term.

Animals↗

PubMed2000

Low doses of dexamethasone suppress pituitary-adrenal function but augment the glycemic response to acute hypoxemia in fetal sheep during late gestation.

Despite the widespread use of antenatal glucocorticoid therapy in obstetric practice, little is known about the effects of synthetic glucocorticoids on the fetal capacity to respond to episodes of acute hypoxemia, such as may occur during labor and delivery. This study investigated the effects of prolonged fetal exposure to low concentrations of dexamethasone on the fetal ACTH, cortisol, and glycemic responses to an episode of acute hypoxemia during the period of dexamethasone treatment in sheep. At 118 d of gestation (term is approximately 145 d), 11 fetal sheep had catheters implanted under halothane anesthesia. From 124 d, five fetuses were infused i.v. continuously with dexamethasone (1.80 +/- 0.15 microg x kg(-1) x h(-1) in 0.9% saline at 0.5 mL/h) for 48 h, and the other six fetuses received saline solution i.v. at the same rate. At 45 h of infusion, acute hypoxemia was induced in all fetuses for 1 h by reducing the maternal inspired fraction of oxygen. During glucocorticoid treatment, fetal plasma dexamethasone concentrations increased to 3.9 +/- 0.2 nM by 24 h and remained elevated for the rest of the infusion period. During hypoxemia, a similar fall in fetal arterial PO2 occurred in both saline-infused and dexamethasone-treated fetuses. In control fetuses, significant increases in plasma ACTH and cortisol concentrations and in blood glucose concentrations occurred during hypoxemia. Dexamethasone treatment prevented the increases in fetal plasma ACTH and cortisol, and augmented the blood glucose response, induced by hypoxemia. These data indicate that prolonged fetal exposure to low concentrations of dexamethasone suppresses pituitary-adrenal function, but augments the glycemic response, to acute hypoxemia in fetal sheep during late gestation.

Acid-Base Equilibrium↗

PubMed2000

Neuropeptide Y in the sheep fetus: effects of acute hypoxemia and dexamethasone during late gestation.

Plasma concentrations of neuropeptide Y (NPY) were measured in pregnant ewes and their fetuses under basal conditions and in response to acute hypoxemia during late gestation. The effects of fetal treatment with dexamethasone on these NPY responses were also examined. Under general anesthesia, 10 Welsh Mountain ewes and their fetuses were chronically instrumented between 117-120 days gestation (dGA; term is approximately 145 dGA) with vascular and amniotic catheters, and an ultrasonic probe around a femoral artery of each fetus. At 124 dGA, five fetuses were continuously infused i.v. with dexamethasone for 48 h at a rate of 1.73 +/- 0.16 microg x kg(-1) x h(-1) while the remaining five fetuses received vehicle at the same rate. At 126 dGA, 45 h from the onset of either infusion, 1 h of materno-fetal hypoxemia was induced by reducing maternal FiO2. During normoxia, maternal plasma NPY concentrations were three times those measured in fetal plasma in both groups. During hypoxemia, PaO2 fell to similar levels in the control and dexamethasone-treated groups in both mothers and fetuses. In control animals, there was a significant increase in the NPY concentration in fetal, but not maternal, plasma during hypoxemia. Fetal treatment with dexamethasone significantly enhanced the fetal NPY response to acute hypoxemia but had no effects on basal NPY levels in the fetal or maternal plasma or on the maternal response to acute hypoxemia. These data show: 1) differences between the maternal and fetal plasma NPY response to maternal inhalation hypoxia; 2) that NPY may play a role in mediating fetal defense responses to acute hypoxemia; and 3) that fetal exposure to glucocorticoids modifies the fetal plasma NPY response to acute hypoxemia.

Animals↗

PubMed2000

Equine uteroplacental metabolism at mid- and late gestation.

Uptakes of oxygen, glucose and lactate by the gravid uterus, fetus and uteroplacental tissues were measured in chronically catheterized pregnant ponies and their fetuses at mid- and late gestation (term 335 days). Rates of O2 uptake by the gravid uterus, fetus and uteroplacental tissues were significant at both gestational ages and were 2- to 3-fold higher in late gestation than the mid-gestation values of 3338+/-794, 1352+/-258 and 2035 +/- 602 micromol min(-1), respectively (n = 4). Similarly, there were significant uptakes of glucose by the gravid uterus, fetus and uteroplacental tissues at both mid- and late gestation. However, unlike O2 uptake, glucose uptake by the uterus and uteroplacental tissues did not increase between mid- and late gestation. No significant uptakes or outputs of lactate were observed by the uterus or uteroplacental tissues at either gestational age, although there was a significant umbilical uptake of lactate in late but not mid-gestation. There was no change in the distribution of uterine O2 uptake between the fetus and uteroplacental tissues with increasing gestational age. The uteroplacental tissues accounted for about 50 % of the uterine O2 uptake at both gestational ages. In contrast, the proportion of the uterine glucose uptake used by the uteroplacental tissues decreased from 73.2+/-2.1 % (n = 5) at mid-gestation to 61.1+/-1.9 % (n = 4, P<0.02) in late gestation. The gestational changes in uteroplacental carbohydrate metabolism in the mare differ from those seen in the ewe and may have important consequences for the duration and outcome of pregnancy in the mare.

Animals↗