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R. J. BARNES
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R. S. COMLINE
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MARIAN SILVER
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Intravascular catheterization of the uterine and umbilical vessels, which was first developed for use chronically in ruminants (Meschia, Cotter, Breathnach & Barron, 1965) has been used in the present acute experiments on pregnant sows (75 to 110 days' gestation). The animals were anaesthetized with sodium pentobarbitone. Vinyl catheters, filled with heparin-saline, were placed in the maternal aorta, vena cava and the uterine veins of each horn. Similar catheters were also inserted into the umbilical artery and vein through placental branches without exposure of either the cord or foetus. The P o2 , P co2 and pH of both the foetal and maternal blood were recorded during each experiment which from the induction of anaesthesia to the final sample usually lasted 5–6 h. In some animals uterine and umbilical blood flows were estimated by the diffusion—equilibrium method of Crenshaw, Huckabee, Curet, Mann & Barron (1968).

Plasma samples were separated immediately and

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A. L. Fowden
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X. Z. Mao
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R. S. Comline
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ABSTRACT

The effects of fetal pancreatectomy on the growth and metabolism of the fetal sheep were investigated in chronically catheterized animals during the last third of gestation. Fetal pancreatectomy reduced body weight and crown–rump length at delivery near term (term 145 days). Body weight was affected more than body length so the ratio of weight to length was significantly less after pancreatectomy than in intact animals (P < 0·05). Pancreatectomized fetuses appeared to maintain a normal growth rate for 5–10 days after surgery but thereafter showed no further significant increase in body weight. When all the data from the intact and pancreatectomized fetuses were combined, there was a significant positive correlation between the plasma insulin concentration in utero and the body weight at delivery near term. The majority of organs studied were reduced in absolute weight after pancreatectomy but only the spleen and thymus were proportionally lighter when the weights were expressed as a percentage of body weight. Brain and placental weights were similar in intact and pancreatectomized fetuses. Over the range of values observed in utero, there were significant inverse correlations between the log plasma insulin level and the mean plasma concentrations of glucose, lactate, fructose and α-amino-nitrogen in individual intact and pancreatectomized fetuses. Insulin infusion into pancreatectomized fetuses restored the metabolite concentrations to their normal values within 48 h of infusion. The results demonstrate that insulin has a vital role in regulating fetal growth and metabolism in utero.

J. Endocr. (1986) 110, 225–231

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P. W. NATHANIELSZ
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MARIAN SILVER
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R. S. COMLINE
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In the lamb, plasma thyroxine concentration changes abruptly during birth. In the foetus, plasma concentration early on the last day of gestation is 6–8 μg thyroxine/100 ml (Nathanielsz, Comline, Silver & Thomas, 1973). Within the first hour after birth plasma thyroxine concentration rises to between 16 and 20 μg/100 ml. It then returns within 3–5 days of birth to levels found in the foetus and remains stable for at least a further 56 days (Nathanielsz, 1970). Since the conversion of thyroxine to tri-iodothyronine may be an important step in the mechanism whereby thyroxine acts on its target tissues, the plasma concentration of tri-iodothyronine during these rapid fluctuations of thyroxine is of interest.

Foetal plasma was obtained by the use of chronic indwelling catheters (Comline & Silver, 1972), and neonatal plasma was obtained by jugular vein puncture. Triiodothyronine was measured by radioimmunoassay using a modification of the method of Hüffner

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M. Silver
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A. L. Fowden
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R. S. Comline
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S. R. Bloom
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ABSTRACT

Plasma glucagon concentrations were measured in chronically catheterized fetal pigs during the last third of gestation and compared with the values observed in anaesthetized fetuses of similar gestational age. The mean plasma concentration of glucagon in the chronically catheterized fetuses was 10·0 ± 1·4 (s.e.m.) pmol/l (n = 11; term = 114 ± 2 days). Concentrations were increased after catheterization and fell to baseline values within 48 h of surgery. Arginine infusion evoked a rapid release of glucagon in chronically catheterized fetuses between 105 and 108 days of gestation; the mean maximum increment in plasma glucagon was 15·4 ± 4·5 pmol/l (n = 5). Plasma glucagon concentrations increased with increasing gestational age in both anaesthetized and chronically catheterized fetuses. Between 95 and 110 days of gestation, glucagon levels were significantly higher in anaesthetized fetuses than in chronically catheterized animals with similar normal pH values. Catheterization and prematurity had no apparent effect on plasma glucagon levels at birth. The plasma concentrations at birth were similar to those observed in the chronically catheterized fetuses in utero provided the piglets did not become acidotic during delivery. Significantly higher plasma levels of glucagon were found in newborn piglets with acidaemia (pH < 7·3) than in piglets with normal pH values at birth (pH > 7·3). When all the data from the newborn piglets were combined, there was a significant negative correlation (r= − 0·79, n = 39, P < 0·01) between blood pH and the plasma concentration of glucagon at birth. These observations demonstrate that the fetal α cells are functional and responsive in utero and at birth.

J. Endocr. (1986) 108, 137–142

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R. S. COMLINE
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L. W. HALL
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R. B. LAVELLE
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P. W. NATHANIELSZ
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MARIAN SILVER
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SUMMARY

Intravascular catheters were placed in the umbilical, uterine and maternal peripheral circulations of 16 Jersey cows between 240 and 260 days of gestation. Foetal plasma cortisol, blood gases and pH, and maternal plasma oestrogen, progesterone and cortisol were measured in ten animals during late pregnancy and throughout spontaneous parturition; all delivered live foetuses although parturition was earlier than normal and the placenta was generally retained. The gradual pre-partum rise in foetal plasma cortisol during the last week of gestation (from 10–20 ng/ml 7 days before parturition to 51 ± 5 ng/ml in the last 3 h before delivery) was much less marked than the abrupt increase immediately after birth when the cortisol concentration invariably doubled. Maternal plasma oestrogen rose from 0.35 ± 0.04 ng/ml to 1·20 ± 0.11 ng/ml during the week before parturition. Progesterone concentrations remained stable until a sudden fall 1–2 days before delivery. The slight alterations in maternal plasma cortisol during this period were not statistically significant. The maternal plasma oestrogen levels were higher in the uterine vein than in the periphery, whereas uterine venous progesterone concentrations were significantly lower than in the peripheral circulation.

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ABIGAIL L. FOWDEN
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R. J. BARNES
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R. S. COMLINE
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MARIAN SILVER
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Insulin secretion and the factors influencing β-cell function were investigated in the chronically catheterized fetal foal and mare during the second half of gestation. The response of the fetal β cells to exogenous glucose was also examined. The mean concentration of insulin in the fetal foal was 7·5 ± 0·5 (s.e.m.) μu./ml (n = 20) which was significantly less than the corresponding maternal value of 49·0 ± 5·0μu./ml (n = 20, P<0·01). The insulin concentration in non-pregnant horses was 24·5 ± 1·5 μu./ml (n = 5) which was significantly less than the value in the pregnant animals (P<0·01). However, there was no significant difference in the mean glucose concentration between the groups of adult animals.

The insulin concentration was related to the endogenous glucose level in both adult and fetal horses. Wide variation in the maternal insulin concentration was observed above a glucose concentration of about 5·0 mmol/l. The mean concentration of insulin in pregnant mares decreased with increasing gestational age while the mean glucose concentration remained unaltered throughout the second half of gestation. There was no change in the basal concentrations of insulin or glucose in the fetus with gestational age although the fetal β-cell response to exogenous glucose appeared to increase with increasing fetal age after 270 days of gestation (term 330 days). There was a significant arterio-venous difference in the concentration of insulin across the gravid uterus in the mare when the arterial insulin level was greater than 30 μu./ml. Below this value, there was no consistent uptake of insulin by the uterus. The observations are discussed in relation to the regulation of insulin release in utero and the effects of pregnancy on maternal β-cell function.

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P. W. NATHANIELSZ
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R. S. COMLINE
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MARIAN SILVER
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A. L. THOMAS
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SUMMARY

Foetal plasma thyroxine levels as well as thyroxine turnover and placental permeability to this hormone were investigated in the conscious pregnant ewe with foetal and maternal intravascular catheters. Foetal plasma thyroxine levels ranged from 4·6 to 6·2 μg/100 ml between 103 days of gestation and the day of birth. Maternal plasma thyroxine levels varied between 2·3 and 4·1 μg/100 ml over the same period. The maternal: foetal ratio across the placenta for thyroxine varied from 0·52 to 0·65. Distribution of radioactive thyroxine injected into the foetal or maternal circulation demonstrated the impermeability of the placenta to thyroxine. Maternal to foetal ratios for labelled thyroxine were 6·2 to 11·9 when injected into the maternal circulation and 0·013 to 0·003 when injected into the foetal circulation. The sheep placenta appears to be capable of actively transporting iodide to maintain a foetal to maternal iodide ratio of up to 8:1.

Foetal thyroxine utilization was of the same order at 111 days of gestation as immediately before parturition when expressed per unit body weight. Utilization of thyroxine per kg by the foetus was about five times that of the mother. Various factors which influence thyroid function are discussed and the activity of the foetal pituitary—thyroid system is compared with other foetal endocrine systems.

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R. J. BARNES
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R. S. COMLINE
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L. B. JEFFCOTT
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M. D. MITCHELL
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P. D. ROSSDALE
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M. SILVER
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SUMMARY

The concentrations of 13,14-dihydro-15-oxo-prostaglandin F (PGFM), the stable metabolite of prostaglandin F, were measured in the plasma of catheterized mares and foetuses and non-catheterized thoroughbred mares and ponies during the last months of gestation. The plasma concentration of PGFM increased gradually towards term in all groups of animals. During the operation for insertion of catheters, maternal and foetal concentrations of PGFM were high, but the values fell to basal levels 24–48 h after the operation. It was found that preoperative starvation (24 h) led to a rise in the concentration oef PGFM in th maternal plasma. The raised concentrations of PGFM during the operation were associated with low progestogen and high oestrogen concentrations in umbilical venous plasma. The subsequent survival period of the catheterized foal was inversely related to the maximum concentration of PGFM attained during the operation.

Changes in the plasma concentration of PGFM were studied during normal parturition in thoroughbred mares, during oxytocin-induced delivery in non-catheterized ponies and during premature delivery or abortion in the catheterized animals. The greatest increase in the concentration of PGFM was seen in the thoroughbred animals during second-stage labour; oxytocin also resulted in a very rapid rise in the level of PGFM, which remained high until delivery. In the catheterized animals, the birth of live foetuses was associated with a rise in the concentration of PGFM in both foetal and maternal plasma during the last 2 h before delivery. Less consistent changes were found during abortion.

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