[Results of the laboratory for in-vitro fertilization of Erasmus University in Rotterdam].
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Biomedical subjects
Publications and source records attributed to C A Jansen.
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Fetal plasma growth hormone concentrations were measured in 15 pregnant ewes over the last 5 days before delivery. In five chronically catheterized pregnant ewes that underwent spontaneous vaginal delivery 146 +/- 2 days (mean +/- SD) of gestation, fetal plasma growth hormone concentrations fell from 124.6 +/- 44.1 ng X ml-1 5 days before delivery to 35.2 +/- 31.3 ng X ml-1 at delivery. In three fetuses in which premature delivery was induced by the infusion of cortisol to the fetus at 128 days of gestation, fetal plasma growth hormone levels fell from 195 +/- 19.1 ng X ml-1 to 70.7 +/- 25.5 ng X ml-1 over the last 5 days of intrauterine life. In seven fetuses in which premature delivery was induced with infusion of synthetic adrenocorticotropin to the fetus beginning at 120 or 130 days of gestation, the fetal plasma growth hormone level did not fall (175.6 +/- 75.7 to 158.9 +/- 60.1 ng X ml-1). Fetal plasma cortisol concentrations at delivery were significantly higher in the cortisol-infused fetuses (214 +/- 38.4 ng X ml-1) than in both control (94.4 +/- 33.7 ng X ml-1) and adrenocorticotropic hormone-infused fetuses (94.5 +/- 31.9 ng X ml-1). The fall in the fetal plasma growth hormone level in cortisol-induced fetuses may be due to the higher fetal plasma cortisol concentrations achieved in the cortisol-infused compared with the adrenocorticotropic hormone-infused fetuses in which no comparable decrease in growth hormone was observed. These findings suggest that there are significant differences in the fetal response to various experimental regimens used for the induction of premature labor in the sheep.
Fetal and maternal plasma ovine chorionic somatomammotropin concentrations have been measured in eight pregnant ewes immediately prior to spontaneous vaginal delivery at 146 +/- 2 gestational days. In seven additional ewes, fetal and maternal plasma ovine chorionic somatomammotropin concentrations were measured immediately before and during induction of premature delivery by infusion of 1 microgram X hr-1 synthetic adrenocorticotropin (ACTH1-24) to the fetus commencing at either 120 to 122 gestational days (n = 3) or 130 to 132 gestational days (n = 4). Both fetal and maternal plasma ovine chorionic somatomammotropin concentrations fell significantly (p less than 0.05) in the 5 days before spontaneous term delivery; no change in the fetal to maternal ratio for plasma ovine chorionic somatomammotropin concentrations was observed. In contrast, the maternal plasma ovine chorionic somatomammotropin concentration rose (p less than 0.05) during infusion of ACTH1-24 to the fetus while the fetal concentration declined. During infusion of ACTH1-24 to the fetus the fetal to maternal ratio for plasma ovine chorionic somatomammotropin concentrations also fell. The finding that the parallel fall in ovine plasma ovine chorionic somatomammotropin concentrations in the fetus and mother in spontaneous term deliveries is not seen following ACTH-induced premature delivery suggests that mechanisms other than activation of the fetal adrenal axis induce the prepartum fall in ovine chorionic somatomammotropin secretion. These findings militate against a role for the fall in ovine chorionic somatomammotropin in the initiation of parturition.
Various pharmacologic agents used in the experimental study of physiologic processes may have pronounced effects on the systems under study. We have studied the effects of xylazine (Rompun) on myometrial activity, fetal and maternal pH, blood gases, heart rate, and fetal breathing movements in chronically catheterized fetal sheep. Xylazine is widely used as a premedication for various forms of animal operations, including the instrumentation of the chronically catheterized fetal sheep preparation. Animals were studied on postoperative day 5. Xylazine had pronounced effects on maternal PaO2 and heart rate that lasted for at least 3 hours. Fetal heart rate and PaO2 returned to preinjection levels within 60 minutes. Myometrial activity doubled in the first 60 minutes after administration of xylazine and did not return to preinjection levels for 3 hours. Fetal diaphragmatic electromyographic activity was almost completely absent in the first and second hours, with a return to normal within 4 hours. These changes were absent in the saline solution-injected control animals. The observed changes in uterine activity and fetal breathing may have been direct effects of xylazine itself or the result of increased uterine activity. The different duration of changes in the ewe and fetus suggests a compensatory mechanism at the uteroplacental level or in the fetoplacental unit.
Measurements of continuous transcutaneous PO2 (tcPO2) have been performed on the scalps of six fetuses from ewes not in labor, while they were under epidural anesthesia. The effects of artifacts such as pressure upon the electrode and pressure on a circle around the electrode (tonsure effect) have been studied. It appears that tcPO2 measurements are markedly influenced by pressure as well as tonsure. As a result, an artificially low tcPO2 reading caused by pressure or tonsure cannot be distinguished from a low value caused by a real decreased intravascular PO2. The "relative heating power" necessary to keep the temperature of the electrode at 44 degrees C is influenced by a number of variables and hence does not solely reflect capillary flow beneath the electrode. Fetal tcPO2 monitoring is unlikely to function as a suitable method of antepartum monitoring throughout delivery in the same manner as the cardiotocograph. The value of dynamic tests at the start of labor such as testing the response to administration of medicaments or gas mixtures needs to be evaluated.
Fetal and maternal plasma concentrations of androstenedione, testosterone, and estradiol were measured in chronically catheterized pregnant sheep during late gestation, spontaneous term delivery, and premature delivery induced by the infusion of low doses of synthetic ACTH-(1-24) (ACTH) to the fetus at 120-130 days gestation. RIAs employing two different antisera directed at different sites of each molecule were used in combination with Celite column chromatography to ensure the specificity of the hormone measurements. Fetal plasma concentrations of all three hormones were greater than the respective maternal concentration at all periods investigated, except immediately before ACTH-induced delivery when fetal testosterone and estradiol concentrations were lower. These observations further support the hypothesis that delivery in the sheep is associated with the induction of placental 17 alpha-hydroxylase and 17,20-lyase by the increased conversion of progesterone to estrogens. The higher values of androstenedione than of testosterone also support the view that estrone is produced in larger quantities than estradiol and that estrone and estrone sulfate are good endocrine markers of the progress of the endocrine changes occurring immediately before parturition in the sheep.
The tenfold increase in red cell 2,3-diphosphoglycerate (DPG) concentration that occurs during the first 5 days of life in lambs is an important adaptation to extrauterine life. In lambs, DPG reduces hemoglobin oxygen affinity by the Bohr effect. Our data on 10 neonatal lambs suggest that the biochemical mechanism underlying this DPG increase involves the following: (1) a rise in plasma glucose from 40 to 100 mg/dl in the first 48 hr of life, which allows for increased glucose consumption in the highly glucose-permeable neonatal RBC; (2) a transitory rise in blood pH begins at birth, peaks at about 20 hr, and falls slightly; (3) the pH increase coincides with a threefold increase in RBC fructose-1,6-diphosphate (FDP) concentration due, we believe, to pH activation of phosphofructokinase; (4) glycolytic intermediates after the glyceraldehyde-3-phosphate dehydrogenase (GAPD) step do not rise in the first 24 hr of life, possibly due to insufficient inorganic phosphate (Pi), a substrate of GAPD; (5) plasma Pi increases from about 7 mg/dl at birth to 11 mg/dl at 72 hr, activates the GAPD, and FDP levels decline; and (6) the in vitro activity of the DPG synthetic enzyme, DPG mutase, is increased 12-fold in neonatal compared to adult RBC. We conclude that the postnatal rise in DPG is explained at least in part by the sequential effects of these metabolic changes.
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Myometrial electromyograms were studied in nonpregnant ewes, pregnant ewes throughout the second half of gestation, and during labor and delivery in normal spontaneous vaginal delivery and premature delivery induced by the continuous infusion of synthetic adrenocorticotropin 1-24, 1 microgram x h-1, to the fetus at 120 and 130 days' gestation. The bursts of electromyographic (EMG) activity during estrus were very similar to those seen in the pregnant ewe in the second half of gestation. In the second half of gestation, the bursts of EMG activity lasted a mean of 6.7 minutes and occurred at intervals of 54.7 minutes in utero, without an incision for fetal instrumentation, and were 7.2 minutes in duration, occurring every 46.6 minutes when the uterus had been incised. EMG activity occurred simultaneously at most recording sites within the uterus. There was no evidence to support the view that a uterine pacemaker exists with a fixed location. As delivery approached, the mean duration of each EMG burst began decreasing more than 24 hours before delivery, and the frequency of the bursts increased, demonstrating that the recording of uterine electromyograms provides a precise and sensitive method for the study of the early changes that lead to labor and delivery.
The switch from fetal to adult hemoglobin (Hb) has been investigated in fetal and newborn lambs. In the period between 125 and 145 days gestation, the proportion of fetal cells containing adult Hb increased significantly in catheterized fetuses. This increase paralleled the rise in fetal plasma cortisol under several different experimental conditions. However, infusion of synthetic adrenocorticotropin (ACTH1-24) into the fetus, which increased fetal plasma cortisol concentrations to levels slightly higher than observed at term, did not bring about any increase in the proportion of cells containing adult Hb. Increasing fetal plasma prolactin (PRL) concentration either by infusion of PRL or by stimulating endogenous PRL release with thyrotropin-releasing hormone (TRH) did not influence the time or rate of the switch. The fetal reticulocyte count was significantly higher in blood samples taken at the time of catheterization in fetuses of 103-115 days gestation than at 116-128 days gestation. In one repeatedly sampled fetus of adult type Hb AB, Hb C was observed at the time when the fetus was anemic. At birth the number of cells containing adult Hb was significantly higher in catheterized lambs than in nonoperated controls.
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A variety of radioimmunoassays specifically characterized for use with fetal and maternal ovine plasma have been used to measure steroid hormone concentrations in small plasma samples drawn simultaneously from mother and fetus. By repeated sampling from the same animal preparation the changes over time of plasma concentrations of cortisol, pregnenolone and its sulphate, and oestrone and oestrone sulphate have been systematically studied. In animals delivering spontaneously at term the fetal plasma cortisol concentration rises between 120 and 130 days gestation and plays an important part in the maturation of several vital physiological systems, including the fetal thyroid axis. In normal term deliveries and premature deliveries induced by synthetic adrenocorticotropin (ACTH(1-24), 1 microgram h-1), the concentration of oestrone sulphate in maternal plasma increases before the fetal plasma concentration. Fetal and maternal oestrogens are probably important in the control of the low-grade tonic myometrial activity that occurs throughout gestation, in the initiation of labour and in the control of uterine blood flow. Low-grade tonic myometrial activity affects fetal oxygenation, fetal breathing and the fetal sleep state and may constitute a pathway through which the mother influences fetal development, with important physiological and possibly pathological consequences.
Continuously monitored carotid arterial PO2 (PaO2) and transcutaneous PO2 (tcPO2) from the scalp of fetuses from ewes not in labor have been compared under epidural anesthesia at different levels of fetal oxygenation. A reasonably good correlation existed between the two readings at normal and high PO2 values. In sharp contrast, at low PaO2 levels there was a considerable bias between the two. Since this bias was variable, the failure of tcPO2 to reflect PaO2 accurately at low PaO2 renders the use of the tcPO2 electrode questionable in the very situation for which it was advocated, namely, the prediction of fetal compromise.
Fetal and neonatal ovine plasma protein and lactate dehydrogenase concentrations have been measured between 124 and 146 days gestation in th chronically catheterized fetal sheep and in the newborn lamb. Fetal plasma protein concentration ranged from 24.7 to 77.0 mg . ml-1 and increased at a rate of 1.65 mg . ml-1 . day-1. In contrast, in the first 10 days of neonatal life plasma protein concentration fell steadilyu at a rate of 2.64 mg . ml-1 . day-1. Fetal plasma lactate dehydrogenase concentration increased at a rate of 0.014 IU . ml-1 . day-1 during the period of study. The increase correlated significantly with the rise of fetal plasma protein concentration. In contrast, in the newborn lamb no significant change in plasma lactate dehydrogenase concentration was observed during ther first 10 days after birth.
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