Fetal Corticosteroid Research Articles

Oestrone, oestradiol-17beta and oestriol levels in human foetal plasma during gestation and at term.

SUMMARY Marked rises in both unconjugated and sulphoconjugated oestrone, oestradiol-17β and oestriol were observed in human foetal plasma between mid-gestation and term. Significant arterio-venous differences for the individual oestrogens in the unconjugated form were found in the umbilical cord plasma. No consistent arterio-venous differences were found for the oestrogen sulphates. This indicates that all three oestrogens are secreted from the placenta into the foetal circulation in the unconjugated form. Mean unconjugated oestrogen (oestrone + oestradiol-17β + oestriol) levels rose from 22·7 ng/ml at 17–20 weeks of gestation to 108·9 ng/ml at term in umbilical venous plasma and from 4·3 ng/ml to 23·3 ng/ml in umbilical arterial plasma. This represents a secretion rate of approximately 30 mg oestrogen/day into the umbilical vein at term. Mean oestrogen sulphate levels rose from 128 ng/ml to 313 ng/ml in the cord plasma during the same period. Of the three oestrogens measured, oestriol was quantitatively the major oestrogen in foetal plasma. It consistently represented about 78% of the unconjugated fraction and 95% of the sulphate fraction at all stages of gestation. The method of delivery did not have a significant effect on the oestrogen levels in uncomplicated pregnancies. Similar oestrogen levels were found in foetal heart blood after either hysterotomy or spontaneous abortion at 16–20 weeks of gestation, and no significant differences were found for oestrogen levels in cord plasma after elective Caesarean section at 38–39 weeks when compared with oestrogen levels after normal delivery at term. A significant rise in foetal unconjugated oestrogens at a time when foetal corticosteroids are increasing may be of physiological importance for foetal maturation in women.

Hormonal Effects on Human Myometrial Activity

Literature on the effects of hormones on human myometrial activity is reviewed. The effects of estrogens, gestagens, and prostaglandins on myometrial activity in pregnant and nonpregnant women, and those of maternal and fetal corticosteroids, biogenic amines, and oxytocin and vasopressin are discussed. Estrogens produce small, frequent, local, and nonpropagated contractions of the myometrium, while gestagens produce contractions of higher amplitude, longer duration, and lower frequency. Maternal and fetal corticosteroids have some importance for myometrial activity of pregnancy in some animals, but their role in humans remains obscure. Epinephrine and norepinephrine stimulate myometrial activity in humans, though their physiologic and therapeutic importance is doubtful. The same holds for serotonin. Oxytocin in large doses stimulates myometrial activity during the proliferative stage of the cycle, but is without effect in smaller doses. During pregnancy, oxytocin progressively stimulates myometrial activity, particularly toward the end of pregnancy. Oxytocin is often used to initiate and stimulate labor. Vasopressin, on the other hand, stimulates myometrial activity during the secretory phase of the cycle, especially around the onset of menstruation. Vasopressin has a less marked effect during pregnancy than oxytocin, and its effects are not enhanced as pregnancy comes to term. The fetus is known to produce considerable amounts of oxytocin and vasopressin during labor, though the significance of this contribution remains to be elucidated. Prostaglandins have a potent stimulatory effect on myometrial activity in both pregnant and nonpregnant women. The possibility that prostaglandins play a physiologic role in the onset of myometrial activity remains to be determined.

Pituitary and Plasma Concentrations of Adrenocorticotrophin, Growth Hormone, Vasopressin and Oxytocin in Fetal and Maternal Sheep during the Latter Half of Gestation and the Response to Haemorrhage

Fetal haemorrhage in exteriorized fetuses of 90 to 143 days conceptual age caused marked increases in fetal plasma ACTH and AVP with maximal values for ACTH at about 40% blood loss and maximal values for AVP with somewhat smaller losses. The rates of rise of ACTH and the maximal values of ACTH were similar to those found in a non-pregnant adult female subjected to haemorrhage. Fetal plasma growth hormones rose in 2 out of 5 animals with no consistent trend in the remainder. In 2 out of 5 animals traces of oxytocin appeared. In two older fetuses in which fetal plasma corticosteroids were determined there was a moderate rise. There was no correlation between maternal and fetal plasma levels with any of the hormones. Fetal ACTH, AVP and growth hormones levels were greatly in excess of those of the mother. Fetal pituitary concentrations of ACTH, oxytocin and neurophysin at all ages were similar to those found in the adult; AVP concentrations were somewhat less. No arginine vasotocin was detected. The high hormone content of the fetal pituitary contrasted with the appearance by light microscopy in the younger animals which showed little evidence for hormone storage. The experiments indicate that the fetal pituitary in the sheep by 90 days is able to synthesize, store and increase several hormones and that haemorrhage is a potent stimulus for the release of ACTH and AVP.

Daily changes in foetal urine and relationships with amniotic and allantoic fluid and maternal plasma during the last two months of pregnancy in conscious, unstressed ewes with chronically implanted catheters.

1. The fluid sacs and bladders of ten foetuses and the allantoic sacs of five foetuses were catheterized between 79 and 96 days gestational age and daily samples were withdrawn until lambs were born naturally at approximately 147 days. Maternal jugular plasma obtained daily allowed the nutritional status of each ewe to be regulated and monitored. All lambs were observed for 7 weeks, and at post-mortem no abnormalities were seen in those operated upon in utero.2. The osmolality, [Na(+)], [K(+)], [Cl(-)], [glucose], [fructose], [urea], [amino acid] and pH of all samples were measured.3. Foetal surgery seemed to affect the actual concentrations of some solutes, but gestational trends in foetal fluid composition were unaltered.4. Until about 7 days before birth the foetal urine osmolality, [Na(+)], [Cl(-)] and [fructose] decreased, its [urea], [amino acid] and pH remained relatively constant, and from about 120 days gestational age the [K(+)] increased. During the last 7 days there was a marked increase in the osmolality and the concentrations of all these solutes, and a decrease in pH.5. Entry of foetal urine into the fluid sacs tended to decrease the osmolality, [Na(+)], [K(+)], [Cl(-)] and [glucose] of both foetal fluids and the [amino acid] of allantoic fluid, and tended to increase the [fructose] and [urea] of both fluids and the [amino acid] of amniotic fluid.6. Changes in urine composition suggested large daily variations in the secretion of foetal antidiuretic hormone and also a rapid increase in its secretion during the last 7 days, and particularly the last 2-4 days before birth.7. Changes in the [Na(+)]/[K(+)] ratios of foetal urine and allantoic fluid were parallel during post-operative recovery, during the course of pregnancy and immediately before birth, and this was consistent with a simultaneous action of foetal plasma corticosteroids on the foetal kidneys and chorioallantois.8. Variations in the [fructose] of foetal urine and allantoic fluid were parallel to changes in their [Na(+)]/[K(+)] ratios and suggested an involvement of foetal corticosteroids in the regulation of the [fructose] of foetal plasma.9. Further evidence has been presented supporting the hypothesis that maternal induced foetal hypoglycaemia effects a relative increase in the secretion of foetal corticosteroids having an action on the chorioallantois. Also, high concentrations of maternal plasma corticosteroids may decrease the permeability of the placenta to glucose.

Daily changes in amniotic and allantoic fluid during the last three months of pregnancy in conscious, unstressed ewes, with catheters in their foetal fluid sacs.

1. Catheters were inserted into the maternal and foetal vasculatures of ten ewes, 100-139 days pregnant, and daily samples of uterine and umbilical blood and maternal jugular vein blood were taken for periods of 5-27 days after operation.2. Catheters were inserted into the fluid sacs of nineteen foetuses, 60-97 days post-conception, and daily samples were withdrawn for up to 90 days from amniotic sacs (eleven foetuses) and for up to 70 days from allantoic sacs (eight foetuses). Maternal jugular plasma was obtained 3 times weekly and an approximation from its composition to that of uterine and umbilical plasma was made using results from the ewes and foetuses with vascular catheters.3. The pH, osmolality, [Na(+)], [K(+)], [Cl(-)], [urea] and [amino acid] of all samples were measured.4. The nutritional status of all ewes was monitored throughout pregnancy. Most lambs were born naturally at approximately 147 days post-conception and their subsequent progress was observed.5. Results at operation and from acute experiments were compared with those from conscious ewes and foetuses of the same gestational age to assess the nature and extent of the influence of the operative procedures on foetal fluid composition. The composition of amniotic fluid was influenced mainly by the anaesthetic and surgical procedures while that of allantoic fluid was affected largely by starvation of the ewe.6. Changes during recovery from operation were followed and indicated that maternal and foetal plasma required about 3 days and the foetal fluids up to 7 days before stability of composition was achieved.7. After recovery from operation, daily changes in the composition of each foetal fluid showed the same general pattern in all foetuses, but the absolute values of constituents sometimes showed large differences.8. It is suggested that flow of foetal urine into the amniotic sac increased from 80 days gestational age, that urine flow into the allantoic sac decreased until about 100 days but did not cease thereafter, and that relative to foetal urine the influence of foetal pulmonary fluid on amniotic fluid composition was not great.9. A relative impermeability of the amnion appeared to be a major factor influencing amniotic fluid composition, whereas pumping mechanisms in the chorioallantois seem to have been responsible largely for changes in the composition of allantoic fluid.10. The quantity of solute relative to that of water within each sac appears to be a major determinant of changes in foetal fluid volumes.11. Changes in the [Na(+)] and [K(+)] of allantoic fluid during the normal course of pregnancy were consistent with an increasing action of mineralo-corticoids on pumping mechanisms in the chorioallantois. Similar but more rapid changes seemed to be associated with acute and chronic episodes of maternal hypoglycaemia. Under these circumstances foetal hypoglycaemia may effect a relative increase in the secretion of foetal corticosteroids having an action on the chorioallantois.12. The results from this study demonstrate clearly the value of using chronically catheterized animals, and it is suggested that their use in physiological studies on the conceptus must eventually supersede that of acute, anaesthetized preparations.