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M E Symonds

Publications and source records attributed to M E Symonds.

At least 55 records · Page 3Linked to original sources
PubMed2001

Responses of the fetal pituitary-adrenal axis to acute and chronic hypoglycemia during late gestation in the sheep.

We investigated the response of the fetal pituitary-adrenal axis to acute and chronic hypoglycemia before and after the normal prepartum activation of this axis at around 135 days gestation (term = 147 +/- 3 days). Pregnant ewes were either well nourished (control group; n = 22) or undernourished (UN; 50% reduction in maternal nutrient intake; n = 23) during the last 30 days of pregnancy. Acute hypoglycemia was induced by intrafetal administration of insulin between 125 and 130 days gestation (control, n = 7; UN, n = 12) and between 138 and 141 days gestation (control, n = 6; UN = 9). Fetal plasma glucose concentrations were significantly lower (P < 0.005) in the UN compared with the control group throughout the insulin infusion period at both gestational age ranges. In the control group, there was no fetal ACTH response to insulin infusion before 135 days gestation, but there was a significant (P < 0.001) response after 136 days gestation. In the UN group, there was a significant ACTH response to insulin infusion both before and after 135 days gestation, and there was no difference in the fetal ACTH response between the two gestational age ranges. The plasma cortisol responses to insulin were greater (P < 0.001) after 136 days compared with before 135 days gestation in both the UN and control groups. In the control group there was no significant relationship between basal fetal plasma ACTH and glucose concentrations between 115-135 days gestation or between 136-145 days gestation. In the UN group, fetal glucose ranged from 0.5-2.0 mM, and plasma ACTH and glucose concentrations were inversely related at 115-135 days gestation [log ACTH = -0.31 (glucose) + 2.21; r = -0.37; P < 0.001] and at 136-145 days gestation [log ACTH = -0.40 (glucose) + 2.50; r = -0.54; P < 0.001]. When the UN and control groups were combined, fetal plasma ACTH concentrations were significantly greater (F = 13.5; P < 0.05) when plasma glucose concentrations were less than 1.0 mM at either 115-135 days or 136-147 days gestation. Similarly, fetal plasma cortisol concentrations were also significantly greater (F = 18.7; P < 0.05) when plasma glucose concentrations were less than 1.0 mM at each gestational age range. Therefore, there is an increased sensitivity of the fetal hypothalamo-pituitary axis to acute falls in glucose concentrations below 1.2 mM after 135 days compared with earlier in gestation. The fetal hypothalamo-pituitary axis can respond, however, when plasma glucose concentrations fall below 1.0 mM, before and after 135 days gestation, independently of whether the low glucose concentrations are a consequence of insulin-induced hypoglycemia or maternal nutrient restriction.

Adrenocorticotropic Hormone↗
PubMed2001

Maternal undernutrition during early to midgestation programs tissue-specific alterations in the expression of the glucocorticoid receptor, 11beta-hydroxysteroid dehydrogenase isoforms, and type 1 angiotensin ii receptor in neonatal sheep.

We have investigated the effects of maternal nutrient restriction in the sheep during the period of rapid placental growth (i.e. 28-77 days gestation; term = 147 days) on feto-placental growth and expression of the glucocorticoid receptor (GR), types 1 and 2 11beta-hydroxysteroid dehydrogenase (11betaHSD1, 11betaHSD2), and types 1 and 2 angiotensin II receptor (AT1, AT2) in fetal and neonatal offspring. Ewes (n = 63) of similar age, body weight, and body composition were randomly allocated to a nutrient-restricted (NR) group in which they consumed 3.2 MJ/day metabolizable energy (ME; equivalent to 50% of predicted requirements) or to a control group in which they consumed 6.7 MJ/day ME (equivalent to 110% of predicted requirements). After 77 days gestation, ewes from both dietary groups consumed close to 100% of ME requirements up to term. Newborn offspring of NR ewes were of similar body weight, but had increased crown-rump length, greater placental weight, and increased placental/body weight ratio (P < 0.01) compared with controls. Their kidneys were heavier (P < 0.05), but shorter in length, with increased ratios of transverse width to length (P < 0.001). GR messenger RNA (mRNA) expression in neonatal offspring from NR ewes was increased in adrenal, kidney, liver, lung, and perirenal adipose tissue (P < 0.01). Conversely, 11betaHSD1 mRNA expression was unaffected, except in perirenal adipose tissue, where it was higher in lambs born to NR ewes (P < 0.01). 11betaHSD2 mRNA expression was decreased in adrenals and kidney (P < 0.001). Maternal NR also resulted in significantly increased AT1 expression in those tissues in which expression of GR was increased and/or 11betaHSD2 was decreased, i.e. adrenals, kidney, liver, and lung. AT2 expression was unaffected by maternal NR. Although 11betaHSD2 mRNA was undetectable in term placenta, it was abundant in midgestation placenta and was lower after maternal NR (P < 0.001). There was close agreement between levels of 11betaHSD enzyme (i.e. 11beta-dehydrogenase and 11-oxoreductase) activities and abundance of 11betaHSD1 mRNA and 11betaHSD2 mRNA expression. The persistence of tissue-specific increases in the expression of GR, 11betaHSD1 and AT1 and decreases in the expression of 11betaHSD2 in adrenals and kidney in newborn offspring in response to a defined period of maternal nutrient restriction during early to midgestation suggests that gene expression has been programmed by nutrient availability to the fetus before birth. These data suggest key potential mechanisms by which maternal nutrition prenatally programs physiological pathways, such as the renin-angiotensin system, in the offspring that may lead to raised blood pressure and other cardiovascular disease risk factors in later life.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2001

Fetal endocrinology and development--manipulation and adaptation to long-term nutritional and environmental challenges.

This article reviews the fetal endocrine system in sheep, a species that has a long gestation and primarily produces a singleton fetus. Attention is focused on information that is applicable to humans. The endocrinology of metabolic homeostasis in sheep fetuses is well adapted to respond to a range of metabolic challenges, including placental restriction and maternal undernutrition. A small placenta results in hypoxaemia, hypoglycaemia, reduced abundance of anabolic hormones, and fetal growth restriction. Fetuses with restricted growth are characterized by tissue-specific reductions in hormone receptor mRNA, for example mRNA for the long form of prolactin receptor is reduced in adipose tissue. In contrast, the adipose tissue of fetuses with accelerated growth, stimulated by increasing maternal nutrition in the second half of gestation, has more protein for the long form of the prolactin receptor and more uncoupling protein 1, by which large amounts of heat are generated at birth. Maternal undernutrition in early gestation, coinciding with the period of rapid placental growth, initially restricts placental growth, but when mothers are fed to requirements, a longer fetus results with a disproportionately large placenta. This nutritional manipulation replicates, in part, epidemiological findings from the Dutch famine of 1944-1945, for which the offspring are at increased risk of adult obesity.

Animal Nutritional Physiological Phenomena↗
PubMed2001

Maternal nutritional manipulation of placental growth and glucose transporter 1 (GLUT-1) abundance in sheep.

Glucose transporter 1 (GLUT-1) is the predominant glucose transporter in the placenta but the extent to which its abundance is nutritionally regulated is unknown. This study investigated the effects of restricted maternal nutrition between day 28 and day 80 of gestation followed by re-feeding to either meet or to exceed the total energy requirements on placental size and GLUT-1 abundance at mid-gestation (that is, day 80) and near to term (that is, days 140-145 of gestation; term = 147 days). Singleton bearing ewes either consumed 8.7-9.9 MJ day(-1) of metabolizable energy (that is, well fed) or 3.2-3.8 MJ day(-1) of metabolizable energy (that is, nutrient restricted) from day 28 to day 80 of gestation, after which stage they consumed either 6.5-7.5 MJ day(-1) (that is, adequately fed) or 8.0-10.9 MJ day(-1) (that is, well fed) of metabolizable energy until near to term. In all ewes, at both sampling dates, the abundance of GLUT-1 was higher in the maternal component than in the fetal component of the placenta. Immunohistochemistry confirmed that GLUT-1 was located in the maternal uterine syncytium. At day 80 of gestation, placental mass was lower (P < 0.05) in the nutrient restricted group, but there was no difference in the abundance of GLUT-1 between the nutrient restricted group and the well fed group. At near term, placental mass was greater (P < 0.05) in ewes that were nutrient restricted during early to mid-gestation and then adequately fed up to term compared with ewes that were well fed during early to mid-gestation. This increase was associated with a higher (P < 0.05) abundance of total placental GLUT-1 and a larger fetus. There was no effect of previous nutrient restriction on placental mass, fetal weight or GLUT-1 abundance at term, when ewes were well fed in the second half of gestation. In conclusion, maternal nutrient restriction between early to mid-gestation alters placental growth but has no effect on placental GLUT-1 abundance. Increasing maternal feed intake to meet calculated energy requirements in previously nutrient restricted ewes during the second half of gestation, increases placental mass and fetal weight, and the abundance of GLUT-1, an adaptation not observed if maternal food intake is increased above requirements.

Analysis of Variance↗
PubMed2000

Influence of thyrotropin-releasing hormone administration at birth on thermoregulation in lambs delivered by cesarean.

OBJECTIVE: We examined the hypothesis that exogenous stimulation with thyrotropin-releasing hormone immediately before umbilical cord clamping can improve thermoregulation in near-term lambs delivered by cesarean. STUDY DESIGN: Twin lambs were injected with either saline solution alone (control, n = 12) or thyrotropin-releasing hormone in saline solution (n = 16) and were immediately placed in a warm (30 degrees C; n = 14) or cool (15 degrees C; n = 14) ambient temperature. In vivo measurements of temperature control (colonic temperature, oxygen consumption, and incidence of shivering) were then performed during the first 6 hours after birth, in conjunction with plasma thyroid hormone measurements. Brown adipose tissue was then sampled for measurement of uncoupling protein 1 abundance. RESULTS: Plasma triiodothyronine concentrations were significantly higher in lambs treated with thyrotropin-releasing hormone than in control lambs between 3 and 6 hours after birth, as were plasma thyroxine concentrations 1 and 5 hours after birth. Delivery temperature had no effect on plasma thyroid hormone concentrations. At 6 hours after birth the abundance of uncoupling protein 1 was higher in lambs treated with thyrotropin-releasing hormone than in control lambs. Lambs treated with thyrotropin-releasing hormone exhibited a lower incidence of shivering than did control lambs between 5 and 6 hours after birth, and an effect of ambient temperature on the incidence of shivering was observed only in the control group. From 3 to 6 hours after birth colonic temperature was significantly higher in cool-delivered lambs treated with thyrotropin-releasing hormone than in the control group. Oxygen consumption was higher in cool-delivered lambs than warm-delivered lambs, but this was not influenced by thyrotropin-releasing hormone. Irrespective of delivery temperature, lambs treated with thyrotropin-releasing hormone possessed more pericardial adipose tissue and hepatic glycogen than did control lambs. CONCLUSION: Thyrotropin-releasing hormone treatment stimulated thyroid hormone secretion in the neonatal lamb and improved thermoregulation during the first 6 hours after birth in near-term lambs delivered by cesarean under cool conditions.

Adipose Tissue, Brown↗
PubMed2000

Maternal nutrient restriction during early to mid gestation alters the relationship between insulin-like growth factor I and bodyweight at term in fetal sheep.

The present study was designed to determine whether altered placental size, as a consequence of maternal nutrient restriction in sheep between 28 and 77 days gestation, is associated with a modified relationship between fetal weight or dimensions and plasma insulin-like growth factor (IGF) I concentration or abundance of hepatic IGF-I and IGF-II mRNA close to term. Singleton-bearing ewes consumed either 1.2x (controls, n = 19) or 0.5x (nutrient restricted, n = 28) their metabolizable energy (ME) requirements from 28 to 77 days gestation, after which all ewes were fed in order to fully meet their ME requirements for maintenance and pregnancy. Close to term (145 +/- 1 days) plasma IGF-I concentration in cord blood was similar between groups, but only significantly correlated with fetal bodyweight, thoracic circumference, crown-rump length and lean body mass in lambs born to control (r2 0.38, 0.76, 0.33, 0.42; P<0.001), and not to nutrient-restricted (r2 = 0.01, 0.11, 0.01, 0.02) ewes. There were no differences in fetal hepatic expression of IGF-I and IGF-II mRNA between groups close to term. In conclusion, maternal nutrient restriction in early to mid gestation followed by feeding to requirements up to term alters the relationship between fetal IGF-I, bodyweight and length. Increasing maternal nutrition in later gestation after a prolonged period of nutrient restriction may stimulate fetal nutrient supply such that fetal growth is enhanced without an increase in plasma IGF-I. As a result, there is a loss of the relationship between fetal weight and plasma IGF-I concentration observed in fetuses whose mothers are fed adequately throughout gestation.

Animals↗
PubMed2000

Influence of relative size at birth on growth and glucose homeostasis in twin lambs during juvenile life.

The effect of differences in size at birth on growth and glucose homeostasis between female twin lambs during juvenile life was examined. Twenty-six sets of twins were entered into the study, of which ten were used for organ sampling at birth and 16 were studied over the first year of life. Eleven sets were defined as being mismatched for birthweight as the weight difference between twins was >25%, with light lambs weighing 4.1 +/- 0.3 kg and heavy lambs weighing 5.1 +/- 0.1 kg. All remaining twins were matched in bodyweight, weighing 4.6 +/- 0.5 kg. During the rapid period of juvenile growth (i.e. one, three and six months of age) and following stabilization of bodyweight (i.e. 12 months of age) glucose tolerance tests were performed by intravenously injecting 0.8 mg kg(-1) bodyweight glucose. This was followed the next day with an insulin tolerance test, performed by intravenously injecting 0.08 units kg(-1) bodyweight insulin. At birth there were no differences in organ weight as a fraction of total bodyweight between matched and mismatched twins, but the ratio of liver to brain weight was lower in light compared with heavy twins. Light lambs remained lighter than their twins up to six months of age, and crown-rump length was also shorter. At one and three months of age there were no differences in basal plasma glucose concentrations between the groups, but glucose tolerance was greater in light compared with heavy lambs at one and six months of age. Insulin tolerance was greater in light compared with matched lambs at one and six months of age. In conclusion, it has been shown that size at birth of one twin in relation to its co-twin is one factor determining glucose regulation during postnatal life. This not only affects glucose and insulin tolerance but also growth over the first six months of age.

Abdomen↗
PubMed2000

Effect of maternal nutrient restriction in early to mid gestation and thyrotrophin-releasing hormone on lamb survival following Caesarean section delivery near to term.

We investigated the influence of restricted maternal nutrition between 28 and 77 days gestation on survival and thermoregulatory adaptation following Caesarean section delivery near to term. This study was designed to examine the hypothesis that adaptation after birth would be compromised in those lambs born to nutrient restricted ewes. We further hypothesised that this would be due in part to inadequate hypothalamic-pituitary-thyroidal function. Lambs born to nutrient restricted ewes were untreated (RU) or treated with thyrotrophin-releasing hormone (TRH; RT) immediately prior to umbilical cord clamping. Single bearing ewes consumed either 6.60 MJ x day(-1) (controls, n = 4) or 3.00 MJ x day(-1) (nutrient restricted, n = 15) from 28-77 days gestation, after which all ewes consumed 7.20 MJ x day(-1). All lambs born to control ewes commenced continuous breathing and began to shiver following Caesarean section delivery and survived to 6 h after birth. Only 4 out of 9 RU lambs established continuous breathing and survived to 6 h after birth compared with all RT lambs. Six hours after birth, RT lambs possessed perirenal brown adipose tissue with a higher thermogenic activity than 6 h old RU or control lambs. Lamb birth weight was similar in all groups. In conclusion, near-term lambs born to ewes nutrient restricted in early to mid gestation are at increased risk of death following Caesarean section delivery. Survival after birth can be significantly enhanced if TRH is administered to the lambs immediately before delivery.

Adaptation, Physiological↗
PubMed2000

Effect of delivery temperature on endocrine stimulation of thermoregulation in lambs born by cesarean section.

We examined the hypothesis that exogenous stimulation with physiological doses of 3,5,3'-triiodothyronine (T(3)) and/or norepinephrine at birth can improve thermoregulation in near-term lambs delivered by cesarean section. This was achieved by investigating the effect of delivery temperature [i.e., warm (30( degrees )C) vs. cool (15( degrees )C) ambient temperatures] on hormonal stimulation on uncoupling protein-1 (UCP1) abundance in brown adipose tissue. In vivo measurements of temperature control (i. e., colonic temperature, oxygen consumption, and incidence of shivering) were made over the first 2.5 h after birth. Each lamb was injected with saline with or without T(3), norepinephrine, or T(3) plus norepinephrine. Irrespective of delivery temperature, abundance of UCP1 increased and incidence of shivering decreased by all hormonal treatments, but this only reduced the rate of decline in colonic temperature of cool-delivered lambs. Oxygen consumption was higher in cool-delivered lambs that were able to fully restore body temperature, an adaptation not observed in controls or any warm-delivered groups. Exogenous administration of endocrine stimulatory factors can enhance the abundance of UCP1 in cesarean-section-delivered lambs with the magnitude of thermoregulatory response being greater at cool than warm delivery temperatures.

Adipose Tissue↗
PubMed2000

Effect of maternal nutrition on brown adipose tissue and its prolactin receptor status in the fetal lamb.

We investigated the influence of maternal nutritional enhancement during the second half of gestation on prolactin receptor (PRLR) abundance in fetal brown adipose tissue (BAT) and liver close to term (i.e. 141-144 d gestation). Ewes were provided with 100% (i.e. control; n = 8) or 150% (i.e. well-fed; n = 7) of their metabolic requirements from 80 to 144 d gestation. Crude plasma membranes were prepared from fetal BAT and hepatic tissue, and individual molecular weight isoforms for the long and short forms of the PRLR were detected by immunoblotting. Mitochondrial preparations were prepared from BAT to measure the amount of the BAT-specific mitochondrial uncoupling protein-1 and its thermogenic activity (i.e. guanosine 5'-diphosphate binding). Fetuses sampled from well-fed ewes were heavier (controls, 3927 +/- 196 g; well-fed, 4783 +/- 219 g; p = 0.01) but possessed less BAT per kilogram body weight (controls, 5.92 +/- 0.43 g/kg; well-fed, 3.85 +/- 0.19 g/kg; p = 0.001), which had a greater uncoupling protein-1 abundance (controls, 56 +/- 5% of reference; well-fed, 78 +/- 9% of reference; p < 0.01) and higher thermogenic activity (controls, 157 +/- 41 pmol guanosine 5'-diphosphate per milligram mitochondrial protein; well-fed, 352 +/- 36 pmol guanosine 5'-diphosphate per milligram mitochondrial protein; p < 0.01) than controls. Multiple isoforms of the long and short forms of the P1LR were detected in all tissues. BAT from well-fed fetuses had a higher abundance of the 15-kD isoform of the long form of the PRLR (controls, 1.6 +/- 0.4 densitometric units; well-fed, 16.3 +/- 2.0 densitometric units; p < 0.001). This isoform was not detected in hepatic tissue. Maternal nutrient intake had no effect on any other isoforms of the PRLR in BAT or liver. In conclusion, increasing the quantity of feed provided in late gestation acts to promote fetal weight and BAT maturation, the combination of which will enhance neonatal viability.

Adipose Tissue, Brown↗
PubMed2000

Maternal nutrition alters the expression of insulin-like growth factors in fetal sheep liver and skeletal muscle.

We investigated the influence of maternal dietary restriction between days 28 and 80 of gestation followed by re-feeding to the intake of well-fed ewes up to 140 days of gestation (term is 147 days) in sheep, on expression of mRNA for insulin-like growth factor (IGF)-I, IGF-II and growth hormone receptor (GHR) in fetal liver and skeletal muscle. Singleton bearing ewes either consumed 3.2-3.8 MJ/day of metabolisable energy (ME) (i.e. nutrient restricted - approximately 60% of ME requirements, taking into account requirements for both ewe maintenance and growth of the conceptus) or 8.7-9.9 MJ/day (i.e. well fed - approximately 150% of ME requirements) between days 28 and 80 of gestation. All ewes were then well fed (150% of ME requirements) up to day 140 of gestation and consumed 8-10.9 MJ/day. At days 80 and 140 of gestation, five ewes were sampled from each group and fetal tissues taken. There was no difference in fetal body weight or liver weights between groups at either sampling date, or skeletal muscle (quadriceps) weight at 140 days. IGF-I mRNA abundance was lower in livers of nutrient-restricted fetuses at day 80 of gestation (nutrient restricted 2.35; well fed 3.70 arbitrary units), but was higher than well-fed fetuses at day 140 of gestation, after 60 days of re-feeding (restricted/re-fed 4.27; well fed 2.83;s.e.d. 0.98 arbitrary units, P=0.061 for dietxage interaction). IGF-II mRNA abundance was consistently higher in livers of nutrient-restricted fetuses (80 days: nutrient restricted 7.78; well fed 5.91; 140 days: restricted/re-fed 7.23; well fed 6.01;s.e.d. 1.09 arbitrary units, P=0.061 for diet). Nutrient restriction had no effect on hepatic GHR mRNA abundance, but re-feeding of previously nutrient-restricted fetuses increased GHR mRNA compared with continuously well-fed fetuses (80 days: nutrient restricted 70.6; well fed 75.1; 140 days: restricted/re-fed 115.7; well fed 89.4;s.e.d. 10.13 arbitrary units, P=0.047 for dietxage interaction). In fetal skeletal muscle, IGF-I mRNA abundance was not influenced by maternal nutrition and decreased with gestation age (P<0.01). IGF-II mRNA abundance was higher in skeletal muscle of nutrient-restricted fetuses compared with well-fed fetuses at day 80 of gestation (nutrient restricted 16.72; well fed 10.53 arbitrary units), but was lower than well-fed fetuses after 60 days of re-feeding (restricted/re-fed 7.77; well fed 13.72;s.e.d. 1.98 arbitrary units, P<0.001 for dietxage interaction). There was no effect of maternal nutrition or gestation age on fetal skeletal muscle GHR expression. In conclusion, maternal nutrient restriction in early to mid gestation with re-feeding thereafter results in alterations in hepatic and skeletal muscle expression of IGF-I, IGF-II and/or GHR in the fetus which may subsequently relate to altered organ and tissue function.

Analysis of Variance↗
PubMed2000

Effect of feeding level and thyroxine on adipose tissue development and growth in postnatal lambs.

We investigated the influence of exogenous thyroxine (T4) administration in conjunction with level of feeding on adipose tissue and liver growth in postnatal lambs. Pairs of lambs were fed either 100 g (i.e. low fed) or 200 g (i.e. high fed) of milk powder per litre of reconstituted milk replacer over the first month of life. Half of the pairs of lambs were fed a bolus dose of T4 (15 mg (kg body weight)-1) daily until 8 days of age. Perirenal adipose tissue and hepatic tissue were sampled at either 8 or 35 days of age. High fed lambs grew faster, possessed more adipose tissue and had larger livers than low fed lambs at 8 and 35 days of age. T4 administration resulted in a lower thermogenic activity (i.e. GDP binding) in adipose tissue at 8 days of age in low, but not high fed lambs. There was no difference between groups in colonic temperature or oxygen consumption. Between 17 and 35 days of age high fed lambs previously treated with T4 had lower daily milk consumption than untreated siblings, but still attained the same growth rate. Plasma insulin-like growth factor-I concentrations were greater in high than low fed lambs, a relationship that was not influenced by T4 treatment. In adipose tissue, iodothyronine 5' deiodinase activity was not influenced by T4 administration and was greater in high than low fed lambs. Hepatic iodothyronine 5' deiodinase activity was not influenced by T4 administration in low fed lambs, but was reduced by T4 in high fed lambs. In conclusion, T4 administration over the first 8 days of life can accelerate the rate of decline in thermogenic activity of uncoupling protein-1. This effect is not observed when the level of feeding is increased. Following withdrawal of T4 treatment, high fed T4-treated lambs were able to maintain the same growth rate as untreated lambs despite having a lower food intake.

Adipose Tissue↗
PubMed1999

The influence of maternal nutrient restriction in early to mid-pregnancy on placental and fetal development in sheep.

Placental weight is a primary factor determining size at birth in many species. In sheep, placental weight peaks at approximately mid-gestation, with structural remodelling occurring over the second half of pregnancy to meet the increasing nutritional demands of the growing fetus. Numerous factors influence placental growth and development in sheep, and many workers (see Kelly, 1992) have investigated the role of maternal nutrition as a regulator of placental and fetal size. We have studied the effects of feeding ewes approximately 50% of their recommended energy requirements during early to mid-pregnancy on fetal and placental indices measured at mid-gestation (i.e. 80 d) and close to term (i.e. 145 d). Maternal nutrient restriction is associated with a reduction in placental weight at 80 d, but an increase in placental weight at 145 d of gestation, compared with ewes fed adequately in early pregnancy. No significant effect on fetal weight was observed at either 80 or 145 d gestation, although differences in body dimensions and the insulin-like growth factor-1 axis were found in lambs from nutrient-restricted ewes delivered close to term. Maternal nutrition during pregnancy plays a pivotal role in the regulation of fetal and placental development in sheep, and therefore has the potential to influence both short- and longer-term health outcomes.

Animals↗
PubMed1999

Effect of maternal dexamethasone treatment and ambient temperature on prolactin receptor abundance in Brown adipose and hepatic tissue in the foetus and new-born lamb.

We investigated the influence of maternal dexamethasone treatment and ambient temperature on prolactin receptor (PRLR) abundance in brown adipose tissue (BAT) and hepatic tissue from foetuses and 6-h-old lambs delivered by caesarean section. Lambs were either delivered into a warm (30 degrees C; WD) or cool (15 degrees C; CD) ambient temperature at 140 days gestation, 2 days after dexamethasone treatment, or at 146 days gestation for controls. Uncoupling protein-1 (UCP1) content of BAT was higher in dexamethasone-treated groups compared to controls. A range of tissue-specific PRLR isoforms was detected. For the long form of PRLR in BAT these isoforms had molecular weights of 66, 54, 34 and 19 kD compared with 88, 76, 66, 58, 54 and 48 kD in liver. In BAT, isoforms of the short form of PRLR had molecular weights of 66, 62, 54, 48, 33 and 31 kD compared with 82, 66, 56, 54, 48, 40 and 33 kD in liver. Dexamethasone treatment in CD lambs resulted in higher abundance of the 54 kD isoform of the short form of PRLR in liver, whilst in BAT dexamethasone resulted in a greater abundance of the 48 kD isoform of the short form, and lower abundance of the 66 kD isoform of the long form of PRLR, compared to controls. A negative correlation (r2 = 0.52) was observed between abundance of 66 kD isoform for the long form of PRLR and UCP1, compared with positive correlations (r2 = 0.58-0.60) for the abundance of the 54 and 48 kD isoforms for the short form of PRLR and UCP1. In conclusion, maternal dexamethasone treatment 1 week before term alters the abundance of PRLR isoforms in a tissue-specific manner. This response is dependent on ambient temperature after birth and may provide a critical endocrine signal for maximising non-shivering thermogenesis.

Adipose Tissue, Brown↗
PubMed1999

Chronic cold exposure has no effect on brown adipose tissue in newborn lambs born to well-fed ewes.

It has been previously shown in twin-bearing ewes fed only 60% of their metabolizable energy requirements for late pregnancy that chronic cold exposure induced by winter shearing of the ewes results in larger lambs with more brown adipose tissue. This effect appears to be primarily due to prevention of a decline in fetal body and tissue weights between 145 days' gestation and 2 h after birth (i.e. 147 days' gestation) in lambs born to underfed shorn ewes. The present study therefore examined the impact, in ewes that were well fed (i.e. received 100% of their metabolizable energy requirements) during the final month of gestation, of chronic cold exposure induced by winter shearing on lamb birthweight and perirenal adipose tissue composition as measured 2 h after birth. Perirenal adipose tissue was analysed for its thermogenic activity (i.e. GDP binding to mitochondria) and catecholamine content. These observations were combined with similar measurements made in near-term (i.e. 145 days' gestation) fetuses sampled from well-fed unshorn ewes. There was no difference between lambs born to shorn or unshorn ewes with respect to birthweight or perirenal adipose tissue weight and composition. Perirenal adipose tissue weight was higher in lambs born to unshorn ewes than in fetuses. The thermogenic activity of adipose tissue was 2-fold higher in lambs born to unshorn ewes compared with 145-day-old fetuses. Epinephrine was detectable only at very low levels in fetal perirenal adipose tissue, increasing 10-fold after birth, with no difference between lambs born to shorn or unshorn ewes. In newborn lambs, plasma growth hormone concentration was lower and insulin concentration higher in shorn compared with unshorn groups. In conclusion, chronic cold exposure induced by winter shearing had no effect on brown adipose tissue development in lambs born to well-fed ewes.

Adipose Tissue, Brown↗
PubMed1999

Abundance of leptin mRNA in fetal adipose tissue is related to fetal body weight.

Leptin mRNA was measured in adipose tissue of fetal sheep by reverse transcription polymerase chain reaction (RTPCR). Abundance of leptin mRNA relative to b-actin mRNA in fetal perirenal adipose tissue increased (P<0.02) with gestation, being higher at 144 d (0.73 +/- 0. 10, n=5) than at 90-91 d (0.40 +/- 0.08, n=6) or 125 d (0.40 +/- 0. 04, n=5) gestation (term approximately 147- 150 d). There was a positive relationship between relative abundance of leptin mRNA (y) and fetal body weight (x)between 90 and 144 d gestation (r 2 =0.27, P<0.01). The slope of the linear dependence of leptin mRNA on fetal weight was 15-fold greater (P<0.001) at 90-91d (y = 2.81x - 1.1, n=6, r 2 =0.71, P<0.025) than between 125-144 d gestation (y = 0.195x - 0.15, n=16, r 2 =0.39, P<0.01). Thus the leptin synthetic capacity of fetal adipose tissue appears to increase in late gestation but this is accompanied by constraint of its sensitivity to fetal body weight. We hypothesise that leptin synthesis in fetal adipose tissue is related to fetal nutrient supply and growth rate.

Adipose Tissue↗