No abstract

No abstract

9. These findings are discussed in relation to existing information on new-born lambs and the human infant during birth.

SUMMARY1. The changes in liver glycogen concentration in normal, adrenalectomized and hypophysectomized foetal lambs have been examined during the last third of gestation using a biopsy technique to remove one or more samples of liver from the same foetus at different gestational ages.2. The rate of glycogen deposition increased sharply from about 130 days' gestation in normal lamb foetuses whereas after hypophysectomy or adrenalectomy liver glycogen concentrations remained low even when gestation was prolonged.3. i.v. infusions of cortisol (4-10 mg/day) for 52 hr resulted in four-to fivefold increases in liver glycogen in all three groups of foetuses. The level of glycogen in the liver appeared to be related to log plasma corticosteroid concentration in all foetuses whether they had received cortisol infusions or not.4. Little or no change occurred in glycogen concentration in other foetal tissues apart from a decrease in the glycogen levels in peri-renal fat of adrenalectomized and hypophysectomized foetuses after cortisol infusion. There were also no detectable changes in foetal plasma lactate, urea or a amino nitrogen following the cortisol infusions. Foetal plasma glucose values rose slightly but this change was significant only in the adrenalectomized group.5. The 52 hr cortisol infusions to the foetus resulted in a slight but significant fall in maternal plasma progesterone in the last few hours of the infusion period.

Insulin secretion and the factors influencing beta-cell function were investigated in the chronically catheterized fetal foal and mare during the second half of gestation. The response of the fetal beta cells to exogenous glucose was also examined. The mean concentration of insulin in the fetal foal was 7.5 +/- 0.5 (S.E.M.) microunit./ml (n = 20) which was significantly less than the corresponding maternal value of 49.0 +/- 5.0 microunit./ml (n = 20, P < 0.01). The insulin concentration in non-pregnant horses was 24.5 +/- 1.5 microunit./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 beta-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 microunits./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 beta-cell function.

SUMMARY1. The experiments were carried out on conscious pregnant Jersey cows with intravascular catheters implanted during late gestation in umbilical and uterine vessels. All but three of fifteen animals delivered live healthy calves.2. Routine daily analyses were made of blood gas tensions, pH and packed cell volume in foetal and maternal blood; plasma concentrations of glucose, fructose, lactate and urea were also determined. Measurements of plasma free fatty acids and blood acetate concentrations were made less frequently. Foetal heart rate and arterial blood pressure were recorded in animals with an umbilical arterial catheter.3. The concentration differences between foetal and maternal blood or plasma in glucose, urea and acetate were measured in fifteen animals. The maternal-to-foetal glucose and acetate gradients across the placenta were high while the foetal-to-maternal plasma urea differences were small.4. In those animals with patent arterial and venous catheters, uterine and umbilical blood flows were measured together with the arteriovenous differences in 02, glucose, acetate and lactate so that rates of foetal and uterine consumption could be estimated. The rates of utilization of 02, glucose and acetate by the foetus were lower than the values for the whole uterus, while the uteroplacental metabolism of these substrates was very high.5. Significant amounts of lactate, which appeared to be produced by the uteroplacental tissue, were utilized by the foetus; the remainder passed into the uterine venous blood.6. The total substrate/02 quotient for the foetus, calculated from the utilization of known metabolites, appeared to be greater than 1. Thus, in the calf some carbon accumulation from sources other than amino acids, the uptake of which was not measured, would seem to occur. These results R. S. COMLINE AND M. SILVER and the metabolic activity of the uterine tissues are discussed in relation to comparable findings in the sheep.

SUMMARY1. Foetal hypophysectomy or bilateral adrenalectomy, carried out in utero at about 100 or 125 days gestation respectively, increased the length of gestation in sheep. It was confirmed that pregnancy was not prolonged significantly if hypophysectomy or adrenalectomy was carried out on one of a pair of twins. The hypophysectomized foetus was, however, smaller and the adrenalectomized foetus larger, than the unoperated twin.2. In about half of the previously operated foetuses intravascular catheters were inserted into both mother and foetus, either at about 125 days, for a comparison with normal catheterized foetuses, or during the postmature period. Both adrenalectomized and hypophysectomized foetuses appeared to have little resistance to stress or infection and the majority survived only 1-2 weeks after the insertion of catheters.3. Maternal peripheral plasma oestrogen, progesterone and corticosteroid concentrations did not appear to be altered by either foetal hypophysectomy or adrenalectomy and were maintained in the normal range during prolonged gestation.4. Foetal plasma oestrogen concentrations were significantly lower after hypophysectomy or adrenalectomy than values found in control lambs. Plasma progesterone values were low in all three groups of foetuses.5. Plasma corticosteroid concentrations after foetal hypophysectomy (12-6 ng/ml.) or adrenalectomy (14-7 ng/ml.) were in the same range as the values for control lambs before the pre-partum rise (14-6 ng/ml.). However, there was a small but significant maternal-to-foetal plasma corticosteroid gradient in the two operated groups whereas this difference was not found in the control animals.6. Tissue glycogen concentrations were measured in non-catheterized adrenalectomized and hypophysectomized foetuses. In these two groups, whether examined before 149 days or after prolonged gestation, liver glycogen concentrations were 30-40 % of those in non-catheterized R. J. BARNES AND OTHERS control foetuses at term. In other respects there was little apparent difference between adrenalectomized and control foetuses.7. Hypophysectomized foetuses had significantly higher glycogen concentrations in heart, skeletal muscle and lung compared with control or adrenalectomized lambs. Plasma glucose and fructose values were also low in this group compared with control foetuses.

Previous investigations on the release of catecholamines from the adrenal medulla of the foetal lamb during asphyxia showed that certain characteristic changes occurred during the development of the foetus (Comline & Silver, 1961). From relatively early in pregnancy, 80-90 days (full term 147 days), the adrenal medulla appeared to react directly to asphyxia with a secretion which contained a high proportion of noradrenaline. This response remained unaffected by section of the splanchnic nerves, destruction of the spinal cord, or by hexamethonium and it appeared to be due to the direct effect of asphyxia on the medullary cells. About 15-20 days before the end of gestation a nervous component was demonstrable, which was dependent upon the integrity of the splanchnic nerves, and the secretion then contained large amounts of both adrenaline and noradrenaline. The mechanism for this response, which at the end of pregnancy superseded the direct effect, appeared to lie in the spinal cord, since section at C 1 made little difference to the secretion.In all these experiments (Comline & Silver, 1961) asphyxia was induced by ligation of the umbilical cord, and at that time it was not practicable either to identify the exact nature of the stimuli responsible for the two types of discharge from the adrenal gland, or to determine whether a relation existed between the level of secretion and the severity of asphyxia in these foetuses. The present investigations have been concerned largely with these problems. The changes of Po2, PC02, pH, lactic acid and glucose in the foetal blood during asphyxia which accompany the discharge from the gland have been examined in lambs at different stages of gestation, and the possible factors involved in the response studied under more carefully controlled conditions. It was soon apparent that the output of catecholamines from the adrenal medulla was primarily affected by a fall in foetal arterial Po2; changes in arterial PC02, pH and lactic acid had little effect. Accurate and rapid measurement of both foetal and maternal