Alterations in oxytocin prohormone processing during early development in the fetal sheep

1992 ◽  
Vol 263 (3) ◽  
pp. R738-R740 ◽  
Author(s):  
M. Morris ◽  
M. Castro ◽  
J. C. Rose
Keyword(s):  
Fetal Development ◽  
Plasma Levels ◽  
Umbilical Artery ◽  
Umbilical Vein ◽  
Late Gestation ◽  
Developmental Changes ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Prohormone Processing ◽  
Specific Antisera

Oxytocin (OT) prohormone processing was studied in fetal sheep. Using specific antisera that recognize the amidated and the COOH-terminal extended forms of OT, we measured arterial and venous levels of the OT peptides in fetal sheep plasma at 94 and 138 days of gestation. Plasma levels of the COOH-terminal extended forms, OT-X, were highest early in development, 35.7 +/- 9.8 vs. 14.3 +/- 5.7 pg/ml (94 vs. 138 days). The ratio of the plasma peptides, OT-X to OT, was higher in the young fetus (35 +/- 11.6 vs. 3.1 +/- 1.3, 94 vs. 138 days). There were also developmental changes in the umbilical artery-umbilical vein differences, with positive values noted in late gestation. These results demonstrate that the changes in the processing of the OT precursor that occur during fetal development are reflected by alterations in the relative amounts of prohormone and amidated hormone found in fetal plasma.

scholarly journals Subpopulations of Corticotrophs in the Sheep Pituitary during Late Gestation: Effects of Development and Placental Restriction

Endocrinology ◽  
2006 ◽  
Vol 147 (10) ◽  
pp. 4762-4771 ◽  
Author(s):  
Kirsten Farrand ◽  
I. Caroline McMillen ◽  
Shigeyasu Tanaka ◽  
Jeffrey Schwartz
Keyword(s):  
Late Gestation ◽  
Mrna Levels ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Pomc Mrna ◽  
Experimental Induction ◽  
Attachment Sites ◽  
Specific Antisera

The prepartum surge in fetal plasma cortisol is essential for the normal timing of parturition in sheep and may result from an increase in the ratio of ACTH to proopiomelanocortin (POMC) in the fetal circulation. In fetuses subjected to experimental induction of placental restriction, the prepartum surge in fetal cortisol is exaggerated, whereas pituitary POMC mRNA levels are decreased, and in vitro, unstimulated ACTH secretion is elevated in corticotrophs nonresponsive to CRH. We therefore investigated the changes in the relative proportions of cells expressing POMC, ACTH, and the CRH type 1 receptor (CRHR1) shortly before birth and during chronic placental insufficiency. Placental restriction (PR) was induced by removal of the majority of placental attachment sites in five ewes before mating. Pituitaries were collected from control and PR fetal sheep at 140 d (control, n = 4; PR, n = 4) and 144 d (control, n = 6; PR, n = 4). Pituitary sections were labeled with specific antisera raised against POMC, ACTH, and CRHR1. Three major subpopulations of corticotrophs were identified that expressed POMC + ACTH + CRHR1, ACTH + CRHR1, or POMC only. The proportion of pituitary corticotrophs expressing POMC + ACTH + CRHR1 decreased (P < 0.05) between 140 (control, 60 ± 1%; PR, 66 ± 4%) and 144 (control, 45 ± 2%; PR, 56 ± 6%) d. A significantly higher (P < 0.05) proportion of corticotrophs expressed POMC + ACTH + CRHR1 in the pituitary of the PR group compared with controls. This study is the first to demonstrate subpopulations of corticotrophs in the fetal sheep pituitary that differentially express POMC, ACTH, and CRHR1 and the separate effects of gestational age and placental restriction on these subpopulations of corticotrophs.

scholarly journals Coordinated changes in hepatic amino acid metabolism and endocrine signals support hepatic glucose production during fetal hypoglycemia

2015 ◽  
Vol 308 (4) ◽  
pp. E306-E314 ◽  
Author(s):  
Satya S. Houin ◽  
Paul J. Rozance ◽  
Laura D. Brown ◽  
William W. Hay ◽  
Randall B. Wilkening ◽  
...  
Keyword(s):  
Fetal Liver ◽  
Hepatic Glucose Production ◽  
Plasma Concentrations ◽  
Glucose Production ◽  
Late Gestation ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Hepatic Glucose ◽  
Molar Percent ◽  
Glucose Output

Reduced fetal glucose supply, induced experimentally or as a result of placental insufficiency, produces an early activation of fetal glucose production. The mechanisms and substrates used to fuel this increased glucose production rate remain unknown. We hypothesized that in response to hypoglycemia, induced experimentally with maternal insulin infusion, the fetal liver would increase uptake of lactate and amino acids (AA), which would combine with hormonal signals to support hepatic glucose production. To test this hypothesis, metabolic studies were done in six late gestation fetal sheep to measure hepatic glucose and substrate flux before (basal) and after [days (d)1 and 4] the start of hypoglycemia. Maternal and fetal glucose concentrations decreased by 50% on d1 and d4 ( P < 0.05). The liver transitioned from net glucose uptake (basal, 5.1 ± 1.5 μmol/min) to output by d4 (2.8 ± 1.4 μmol/min; P < 0.05 vs. basal). The [U-13C]glucose tracer molar percent excess ratio across the liver decreased over the same period (basal: 0.98 ± 0.01, vs. d4: 0.89 ± 0.01, P < 0.05). Total hepatic AA uptake, but not lactate or pyruvate uptake, increased by threefold on d1 ( P < 0.05) and remained elevated throughout the study. This AA uptake was driven largely by decreased glutamate output and increased glycine uptake. Fetal plasma concentrations of insulin were 50% lower, while cortisol and glucagon concentrations increased 56 and 86% during hypoglycemia ( P < 0.05 for basal vs. d4). Thus increased hepatic AA uptake, rather than pyruvate or lactate uptake, and decreased fetal plasma insulin and increased cortisol and glucagon concentrations occur simultaneously with increased fetal hepatic glucose output in response to fetal hypoglycemia.

Carnitine in the Perinatal Metabolism of Lipids I. Relationship Between Maternal and Fetal Plasma Levels of Carnitine and Acylcarnitines

PEDIATRICS ◽  
1981 ◽  
Vol 67 (1) ◽  
pp. 95-100
Author(s):  
Milan Novak ◽  
Ellen F. Monkus ◽  
Dina Chung ◽  
Maria Buch
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Plasma Levels ◽  
Umbilical Vein ◽  
Maternal Plasma ◽  
Free Carnitine ◽  
Acid Oxidation ◽  
Limited Capacity ◽  
Fetal Plasma ◽  
Arterial Plasma

Since premature infants have a limited capacity for fatty acid oxidation, supplementation with carnitine may improve their utilization of fat. Documentation of the source and extent of fetal carnitine reserves should explain the possible need for exogenous carnitine in the neonate. Correlation between free carnitine concentration in maternal and umbilical arterial plasma at birth (r = .45, P &lt; .01) indicates that the initial concentration of free carnitine in the newborn depends on the maternal level. Thin-layer chromatography shows more γ-butyrobetaine in maternal than umbilical arterial plasma indicating higher availability of the precursor of carnitine biosynthesis. Elevated fatty acid oxidation in maternal tissues seems to be reflected by larger amounts of long-chain acylcarnitines in maternal plasma. Shortchain acylcarnitines, mainly acetylcarnitine, are higher in the umbilical vein than in maternal plasma (P &lt; .01) indicating that the conceptus (the placenta or fetus) is either producing more or utilizing less acetylcarnitine. Plasma levels of carnitine rapidly decrease in premature newborns during the first three days after birth if no exogenous carnitine is given (P &lt; .001), while no significant changes of total carnitine were detected in adult patients on total parenteral alimentation for one week. This difference indicates lower carnitine depots or limited capacity for carnitine biosynthesis in neonates. The possibility still requires further investigation that the development of the optimal rate of fatty acid oxidation in human newborns, as well as in other newborn mammals, may depend on the supply of exogenous carnitine.

Effect of alteration of maternal plasma progesterone concentrations on fetal behavioural state during late gestation

1997 ◽  
Vol 152 (3) ◽  
pp. 379-386 ◽  
Author(s):  
M B Nicol ◽  
J J Hirst ◽  
D Walker ◽  
G D Thorburn
Keyword(s):  
Plasma Concentrations ◽  
Maternal Plasma ◽  
Late Gestation ◽  
Emg Activity ◽  
Fetal Sheep ◽  
Plasma Progesterone ◽  
Fetal Plasma ◽  
Progesterone Synthesis ◽  
Progesterone Metabolites ◽  
Vascular Catheters

Placental progesterone synthesis exposes the fetus to high levels of progesterone and progesterone metabolites during late gestation which may influence fetal behaviour. To determine the role of maternal progesterone synthesis in the control of fetal arousal state and fetal breathing movements (FBM), the effect of raising and lowering maternal progesterone concentrations was examined in chronically catheterised fetal sheep. Fetal and maternal vascular catheters, fetal tracheal and amniotic fluid catheters as well as electrodes for recording fetal electrocortical (ECoG), electro-ocular (EOG) and nuchal muscle electromyographic (EMG) activity were implanted between 118 and 122 days gestational age (GA). Progesterone, 100 mg, administered twice daily i.m. for 3 days (130–133 days GA) resulted in a marked elevation in maternal plasma progesterone concentrations (370 ± 121%, n=5, P<0·05), but had no effect on fetal plasma concentrations. Fetal EOG episodes and the duration of fetal behavioural arousal were significantly suppressed throughout the progesterone treatment period (74·4–81·1% and 58–65% respectively, P<0·05, n=5). Four ewes received Trilostane (25 mg i.v.), a 3β-hydroxysteroid dehydrogenase inhibitor, between 136 and 140 days GA. Maternal and fetal progesterone concentrations were significantly lowered by 60 min after treatment (19·8 ± 8·0% and 39·5 ± 24·3% respectively, P<0·05). The incidence of fetal EOG activity increased from a pretreatment level of 26·8 ± 1·5 min/h to 30·3 ± 2·8 min/h at 1–6 h and to 35·0 ± 1·7 min/h (P<0·05) during the 7–12 h after Trilostane treatment. The duration of FBM episodes was significantly higher at 1–6 h and 7–12 h after Trilostane treatment (19·5 ± 3·0 and 23·6 ± 5·5 min/h respectively, P<0·05) compared with pretreatment levels (11·2 ± 1·2 min/h). We conclude that increasing maternal progesterone levels suppresses fetal EOG activity and behavioural arousal, whereas reducing maternal progesterone synthesis leads to an elevation of EOG activity and FBM. Journal of Endocrinology (1997) 152, 379–386

Blood pressure and heart rate in the ovine fetus: ontogenic changes and effects of fetal adrenalectomy

1999 ◽  
Vol 276 (1) ◽  
pp. H248-H256 ◽  
Author(s):  
Nobuya Unno ◽  
Chi H. Wong ◽  
Susan L. Jenkins ◽  
Richard A. Wentworth ◽  
Xiu-Ying Ding ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Plasma Cortisol ◽  
Time Windows ◽  
Late Gestation ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Long Term Study ◽  
Arterial Blood ◽  
Ovine Fetus

Ontogenic changes in baseline and 24-h rhythms of fetal arterial blood pressure (FABP) and heart rate (FHR) and their regulation by the fetal adrenal were studied in 18 fetal sheep chronically instrumented at 109–114 days gestation (GA). In the long-term study, FABP and FHR were continuously recorded from 120 days GA to spontaneous term labor (>145 days GA) in five animals. Peak times (PT) and amplitudes (Amp) of cosinor analysis were compared at 120–126, 127–133, and 134–140 days GA. Consistent, significant linear increases in FABP and linear decreases in FHR were observed in all fetuses. Significant 24-h rhythms in FABP and FHR were observed during all the time windows. In the adrenalectomy study, to test the hypothesis that fetal cortisol plays a key role in cardiovascular maturation, fetal adrenals were removed in eight animals (ADX); sham fetal adrenalectomy was performed on five animals (Con). Cortisol (4 μg/min) was infused intravenously in four ADX fetuses from day 7postsurgery for 7 days (ADX+F). No significant changes in PT and Amp in FABP and FHR were observed. Plasma cortisol levels remained low in Con and ADX fetuses (<4.9 ng/ml). Cortisol infusion increased fetal plasma cortisol to 22.3 ± 3.2 ng/ml (mean ± SE) on day 13 in ADX+F fetuses. FABP increased in control and ADX+F but not ADX fetuses; FHR decreased in control and ADX but rose in ADX+F fetuses. These results suggest that, in chronically instrumented fetal sheep at late gestation, 1) increases in FABP and decreases in FHR are maintained consistently from 120 to 140 days GA, with distinct 24-h rhythms, the PT and Amp of which remain unchanged, and 2) the physiological increase in FABP is dependent on the fetal adrenal; bilateral removal of the fetal adrenals does not prevent the ability of cortisol to produce a sustained increase in FABP.

Arginine vasopressin responses to hypoxia and hypercapnia in late-gestation fetal sheep

1991 ◽  
Vol 260 (6) ◽  
pp. R1077-R1081 ◽  
Author(s):  
H. Raff ◽  
C. W. Kane ◽  
C. E. Wood
Keyword(s):  
Arginine Vasopressin ◽  
Late Gestation ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Hypoxic Conditions ◽  
Arterial Ph ◽  
Hypercapnic Hypoxia ◽  
Per Se ◽  
Peripheral Arterial

The purpose of this study was to determine the interaction of hypoxia and hypercapnia in the control of arginine vasopressin (AVP) secretion in fetal sheep and to determine the role of the peripheral arterial chemoreceptors in that response. We measured the plasma AVP response to hypercapnia and/or hypoxia in catheterized intact or sinoaortic-denervated fetal sheep between 123 and 144 days of gestation. Ewes were exposed to the following inspired gases: two successive 30-min periods of normocapnic normoxia, 30 min of normocapnic normoxia followed by 30 min of normocapnic hypoxia, two successive 30-min periods of hypercapnic normoxia, or 30 min of hypercapnic normoxia followed by 30 min of hypercapnic hypoxia (i.e., asphyxia). Hypercapnia per se had no significant effect on fetal plasma AVP. Normocapnic hypoxia per se resulted in a significant increase in fetal plasma AVP. Although hypercapnia resulted in a significant acidemia, the decrease in arterial pH was more marked under hypoxic conditions. Hypercapnia/acidemia augmented the AVP response to hypoxia. Fetal sinoaortic denervation did not significantly attenuate any of the AVP responses. We conclude that hypercapnia augments the fetal AVP response to hypoxia and that the AVP response to neither normocapnic nor hypercapnic hypoxia is dependent on afferent information carried in the carotid sinus or aortic nerves.

GRF treatment of late pregnant ewes alters maternal and fetal somatotropic axis activity

1991 ◽  
Vol 260 (4) ◽  
pp. E575-E580 ◽  
Author(s):  
M. M. Blanchard ◽  
C. G. Goodyer ◽  
J. Charrier ◽  
G. Kann ◽  
R. Garcia-Villar ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Late Gestation ◽  
Placental Lactogen ◽  
Maximal Response ◽  
Pituitary Cells ◽  
In Vitro Test ◽  
Fetal Sheep ◽  
Igf I

To examine the effects of anabolic agents given during late gestation on the maternal and fetal somatotropic axes, we injected pregnant ewes twice daily with 0.15 mg somatocrinin (GRF)-(1-29) for 10 days beginning on day 130 of gestation. Maternal and fetal endocrine changes were compared with control animals using both in vivo and in vitro approaches. Treatment with GRF increased maternal plasma levels of growth hormone (GH) and insulin-like growth factor I (IGF-I;P less than 0.05) but not IGF-II. Under in vitro test conditions, maternal pituitary cells showed a greater maximal response (P less than 0.001) to GRF. In the fetuses of treated ewes, cord plasma GH levels were not significantly increased compared with controls. These animals had similar IGF-I but higher IGF-II (P less than 0.05) plasma levels. The maximal response of fetal pituitary cells to GRF was increased (P less than 0.001). GRF treatment had no influence on maternal and fetal pituitary cell responses to somatostatin under either basal or GRF-stimulated conditions. In addition, these treatments did not affect plasma levels of placental lactogen, glucose, or free fatty acids in the maternal and fetal sheep. These data are compatible with the hypothesis that treatment of pregnant ewes in the last days of gestation with GRF could support accelerated fetal growth.

Placental norepinephrine clearance: in vivo measurement and physiological role

1995 ◽  
Vol 269 (1) ◽  
pp. E145-E149 ◽  
Author(s):  
L. Bzoskie ◽  
L. Blount ◽  
K. Kashiwai ◽  
Y. T. Tseng ◽  
W. W. Hay ◽  
...  
Keyword(s):  
Production Rate ◽  
Umbilical Vein ◽  
Physiological Role ◽  
Total Clearance ◽  
Clearance Rates ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
In Vivo Measurement ◽  
A Site

The intrauterine clearance rate of catecholamines is higher than in newborn animals or in adults. The separate contributions of the fetus and placenta to this clearance are not known. The placenta is a site of expression of the amine plasma membrane transporters that mediate this process. To determine the physiological role of this placental transporter in vivo, we studied fetal sheep at 123 days with common umbilical vein (UV), fetal arterial (AO), and venous catheters. Tritiated norepinephrine ([3H]NE) was infused to determine the kinetics of placental and fetal NE appearance and clearance rates. Umbilical flow was determined by [3H]NE infusion. Placental and total (fetal-placental) NE clearance rates were determined by measurement of [3H]NE from simultaneously drawn UV and AO samples. Total clearance was 99 +/- 8 ml.kg-1.min-1. Placental fractional [3H]NE extraction was 21% and accounted for 48% of total clearance. Fetal plasma NE production rate was 85 +/- 20 ng.kg-1.min-1. We conclude that placental catecholamine clearance is an important metabolic function of the placenta. This mechanism for clearance of the high fetal production rate of catecholamines is vital for fetal homeostasis. We speculate that derangements in placental catecholamine clearance may explain the exaggerated adverse effects on the fetus of drugs like cocaine, which block catecholamine transport.

Sinoaortic denervation attenuates the reflex responses to hypotension in fetal sheep

1989 ◽  
Vol 256 (5) ◽  
pp. R1103-R1110 ◽  
Author(s):  
C. E. Wood
Keyword(s):  
Heart Rate ◽  
Fetal Heart ◽  
Carotid Sinus ◽  
Late Gestation ◽  
Plasma Acth ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Venae Cavae ◽  
Afferent Fibers ◽  
Vascular Catheters

Hypotension in fetal sheep stimulates reflex decreases in heart rate and increases in the secretion of several hormones, including adrenocorticotropin (ACTH), cortisol, vasopressin, and renin. However, little is known about the afferent limb(s) of the reflex(es) controlling these responses. Fetal sheep between 122 and 134 days gestation were prepared with chronic vascular catheters, intravascular balloon-tipped catheters, and amniotic fluid catheters. Seven fetal sheep were also subjected to sinoaortic denervation, and nine remained intact. After recovery from surgery for 2-5 days, fetuses were subjected to a 10-min period of hypotension produced by vena caval obstruction, produced by inflation of balloons in the superior and inferior venae cavae. Vena caval obstruction produced decreases in fetal heart rate and increases in fetal plasma ACTH, vasopressin, and renin activity, which were related to the degree of hypotension. Prior sinoaortic denervation attenuated all of these responses. It is concluded that afferent fibers in the carotid sinus and/or aortic depressor nerves mediate part of the heart rate, ACTH, vasopressin, and renin responses to vena caval obstruction in late-gestation fetal sheep.

Reduced glucose-stimulated insulin secretion following a one-week IGF-1 infusion in late gestation fetal sheep is due to an intrinsic islet defect

2021 ◽  
Author(s):  
Alicia White ◽  
Jane Stremming ◽  
Brit H Boehmer ◽  
Eileen Chang ◽  
Sonnet S. Jonker ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Plasma Insulin ◽  
Cell Function ◽  
Late Gestation ◽  
Igf Binding Proteins ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Glucose Stimulated Insulin Secretion ◽  
Fetal Islets

Insulin and insulin-like growth factor-1 (IGF-1) are fetal hormones critical to establishing normal fetal growth. Experimentally elevated IGF-1 concentrations during late gestation increase fetal weight but lower fetal plasma insulin concentrations. We therefore hypothesized that infusion of an IGF-1 analog for one week into late gestation fetal sheep would attenuate fetal glucose-stimulated insulin secretion (GSIS) and insulin secretion in islets isolated from these fetuses. Late gestation fetal sheep received infusions with IGF-1 LR3 (IGF-1, n=8), an analogue of IGF-1 with low affinity for the IGF binding proteins and high affinity for the IGF-1 receptor, or vehicle control (CON, n=9). Fetal GSIS was measured with a hyperglycemic clamp (IGF-1, n=8; CON, n=7). Fetal islets were isolated, and insulin secretion was assayed in static incubations (IGF-1, n=8; CON, n=7). Plasma insulin and glucose concentrations in IGF-1 fetuses were lower compared to CON (P=0.0135 and P=0.0012, respectively). During the GSIS study, IGF-1 fetuses had lower insulin secretion compared to CON (P=0.0453). In vitro, glucose-stimulated insulin secretion remained lower in islets isolated from IGF-1 fetuses (P=0.0447). In summary, IGF-1 LR3 infusion for one week into fetal sheep lowers insulin concentrations and reduces fetal GSIS. Impaired insulin secretion persists in isolated fetal islets indicating an intrinsic islet defect in insulin release when exposed to IGF-1 LR3 infusion for one week. We speculate this alteration in the insulin/IGF-1 axis contributes to the long-term reduction in β-cell function in neonates born with elevated IGF-1 concentrations following pregnancies complicated by diabetes or other conditions associated with fetal overgrowth.

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