Contribution of maternal circulation to blood-borne progesterone in the fetus. I. Studies on human subjects

Tritiated progesterone was infused intravenously at a constant rate into three pregnant volunteers in labor, for at least two hours before delivery. Blood samples from a maternal peripheral vein and from unbilical vessels were taken at birth. Comparison of the specific activities of progesterone in these samples indicated that 10 per cent or less of the hormone in fetal circulation is derived from transfer of maternally circulating progesterone. After consideration of reported values of umbilical vein blood flow at term and measured arteriovenous differences in concentrations of progesterone in umbilical vessels, the secretion rate of the placental hormone toward the fetus was estimated to be about 1/10 of the rate of secretion of progesterone toward the maternal circulation. About 1 per cent of the maternally circulating hormone was found to cross the placenta.     

Partition of maternal nutrients to the placenta and fetus in the sheep

Utilizing the Fick Principle, the fluxes of oxygen and glucose leaving the uterine circulation and entering the fetal umbilical circulation were measured simultaneously in 35 chronically catheterized sheep. Additionally, the distribution of placentally produced lactate into the uterine and umbilical circulations was measured by the same techniques. Under unstressed conditions, placental oxygen consumption accounted for approximately half the oxygen exiting the uterine circulation. Placental glucose consumption averaged 75% of the glucose exiting the uterine circulation, and this proportion increased with decreasing glucose concentration in the maternal artery. Lactate was produced at a high rate by all placentae, and distributed disproportionately to the fetus, in spite of higher fetal lactate concentration.Fetal metabolism was aerobic, as demonstrated by a high rate of net oxygen consumption and a high rate of net lactate consumption. Fetal oxygen metabolism correlated well with fetal weight and with the sum of net fetal lactate and glucose consumption.     

Circulatory response to atropine in sheep fetus.

Atropine was given to the semichronic sheep fetus intravenously. Fetal heart rate, fetal perfusion pressure, and carotid blood flow increased. Cerebral blood flow was measured with the radioactive microsphere technique. Atropine was capable of increasing the cerebral blood flow. Elevation of carbon dioxide also caused an increase in cerebral blood flow, adding to the effect of atropine.     

Studies of circulation and acid-base balance in pregnant sheep: II. The effect of magnesium sulfate infusion

Ten infusions of magnesium sulfate, in clinical doses for toxemia therapy, were administered to seven chronically catheterized ewes at 109-126 days' gestation. Maternal and fetal Mg++ concentrations in arterial serum indicated hindered placental passage. A significant decrease in maternal arterial oxygen pressure and hemoglobin was seen at 15 minutes. A significant increase in maternal arterial carbon dioxide pressure and transient maternal hypotension and tachycardia were seen at five minutes. Fetal effects of maternal infusion were minimal and transient. All maternal and fetal parameters returned to control levels by 90 minutes.     

The effect of acute maternal hypoxia on fetal oxygenation and the umbilical circulation in the sheep

The mean oxygen consumption was 8.4 ± 1.9 ml/min/kg in the near-term fetal sheep. In response to acute maternal hypoxia fetal O₂ consumption decreased to lower than 50% of the control values. The decrease was rapidly instituted, proportional to the degree of hypoxia, sustained for up to 47 min and stable over this period. With increasing duration of hypoxia, a progressive metabolic acidosis developed. Recovery of oxygen consumption occurred rapidly after hypoxia ceased, though the acidosis was not resolved until 2 h later. Umbilical blood flow was maintained during maternal hypoxia and umbilical arterial and venous pressures increased. A fetal bradycardia invariably accompanied the hypoxia.     

The route of maternal IgM transport to the rabbit fetus.

The route of IgM transport to the rabbit fetus was investigated by comparing its localization with that of IgG in the yolk sac splanchnopleure and uterine tissues using direct immunofluorescence and immunodiffusion analysis. IgM was first detected in fetal serum at 20 days of gestation but was present in uterine fluid at 18 days, the earliest stage tissues and fluids were examined. IgM was co-localized with IgG in the yolk sac endoderm basement membrane and in the vascular mesenchyme of the yolk sac splanchnopleure providing evidence of its transport to fetal blood; it was also present in vesicles in the yolk sac endoderm. IgM could not be detected in uterine fluid of nonpregnant uterine horns of rabbits unilaterally pregnant. Human IgM injected into the maternal circulation was readily transported to the uterine fluid and across the yolk sac splanchnopleure to fetal blood indicating that IgM secreting plasma cells, found to be present in the uterine stroma, contributed little towards IgM in the uterine fluid. Degenerating paraplacental decidual tissue, a feature of rabbit pregnancy, is suggested to be a major route for maternal immunoglobulin transport to the uterine fluid.     

Fetal cells in the maternal circulation.

The analysis of fetal cells from the maternal circulation would be the least invasive method of prenatal diagnosis. Potential fetal cell types to enter the maternal circulation are lymphocytes, trophoblast cells and nucleated erythrocytes. With conventional methods, such as cytology and interphase or metaphase cytogenetics, the ratio of fetal to maternal cells was overestimated in the past. Currently most groups use polymerase chain reaction-based Y-sequence analysis for the detection of fetal cells in pregnancies with male fetuses, either with or without prior enrichment of fetal cells. For fetal cell separation, fluorescence-activated cell sorting and immunomagnetic beads have been applied, and recently our group has used discontinuous density gradient centrifugation for this purpose. We have shown that the transferrin receptor antigen alone is not sufficient for enrichment of fetal nucleated erythrocytes. Despite some initial promising results with fluorescence in situ hybridization, the reproducibility and reliability of the techniques are still limited, mainly due to the lack of very specific cell markers and the very low and variable concentrations of fetal cells among numerous maternal cells.     

The influence of maternal psychological stress on the fetus.

The effects of maternal agitation, induced by exposure to bright light, upon fetal well-being were studied in pregnant rhesus monkeys at 139 to 148 days of gestation. Fetuses were classified as "healthy" or "asphyxiated" according to their initial acid-base state. Following variable periods of maternal excitement, a decrease in heart rate and arterial oxygenation was seen in all fetuses. Recovery occurred more rapidly in the healthy group, after maternal sedation was achieved, either by removing the stimulus or by additional administration of pentobarbital, 5 to 20 mg. intravenously. The beneficial effects of meternal sedation on the fetus have thus been demonstrated.     

Fetal breathing and adaptation to maternal hemorrhage in the sheep.

The effect of maternal hemorrhage in chronic preparations was studied on fetal lambs in the last month of gestation. Fourteen to 20 per cent of maternal blood was estimated to have been removed within 30 minutes, which resulted in a drop of 30 per cent of mean maternal arterial pressure. A fetal bradycardia started 28 +/- 13 minutes after the beginning of maternal hemorrhage. It lasted 30 +/- 15 minutes and was concomitant with a rise in fetal arterial pressure. It was followed by a long-lasting fetal tachycardia of 130 +/- 38 minutes and was corrected only by reinfusion of blood to the mother. The fetal blood gases demonstrated a mild asphyxia with a persistent metabolic acidemia until reinfusion of blood to the mother. Maternal and fetal plasma cortisol levels rose significantly at the end of the hemorrhage. Tracheal fluid flow did not change. Fetal breathing recorded 20 hours before and 24 hours after the experiment did not show consistent changes, but during fetal bradycardia there was no fetal breathing. Recent clinical investigations in this field have been made in the human fetus to estimate standards of fetal well being. These peculiar animal experiments do not show any significant improvement by recording fetal breathing over the recording of prelabor fetal heart rate.     

Is maternal alkalosis harmful to the fetus?

Normal pregnancy is characterized by a compensated respiratory alkalosis. The effect of maternal alkalosis on the fetus is less well understood than the more common problem of maternal acidosis. We present a case of maternal alkalosis, complicated by bronchial asthma, in which the fetus was stillborn. The pathophysiology of this condition is discussed with data to support the potential harm of maternal alkalosis in pregnancies complicated by a fetus with borderline reserve. In such instances, the fetus should be carefully monitored and consideration might be given to therapy such as the use of acetozolomide, discouraging hyperventilation by the mother and even early delivery of the fetus.     

T细胞免疫参与母-胎免疫调节的研究进展

母-胎免疫调节中T细胞免疫起着重要作用,CD4+CD25+调节性T细胞(CD4+CD25+Treg细胞)、Th1/Th2型细胞因子、T细胞表达的CTLA-4是研究热点,孕早期CD4+CD25+调节性T细胞由外周血向母-胎界面迁移,妊娠期间外周血存在调节性T细胞数量的扩增,尤其是FOXP3+调节性T细胞的数量及免疫抑制活性对母-胎免疫调节起重要作用。协同刺激分子CTLA-4对T细胞免疫有负性调节作用,与Th型细胞因子、调节性T细胞之间相互联系、相互作用,共同参与母-胎免疫调节。