Showing papers on "Fetus published in 1976"

Body composition of the reference fetus

Abstract: Published data from chemical analyses of human fetuses have been utilized to construct a reference fetus of representative body composition. For gestational ages 24 through 40 weeks, body composition of the reference fetus is presented, including water, lipid, protein and major minerals. Concentrations of water, sodium, and chloride per unit of body weight decrease with increasing gestational age, whereas those of protein, lipid, calcium, phosphorus, magnesium and potassium increase. From the estimates of body composition at each age and from the gain in body weight, composition of gain and daily increments of body components have been calculated.

Umbilical uptake of amino acids in the unstressed fetal lamb.

Abstract: The whole blood concentrations of 22 amino acids were measured in a chronic, unstressed fetal lamb preparations. Samples were taken daily from the umbilical artery, umbilical vein, and maternal artery over the latter quarter of gestation. 73 sets of samples (from the umbilical artery and vein and the maternal artery) from 13 animals were analyzed for amino acid levels. Oxygen contents were determined simultaneously in 48 sets (umbilical artery and vein) to relate fetal oxygen consumption to amino acid uptake via the umbilical circulation. The results indicate that there is no umbilical uptake of the acidic amino acids, glutamate and aspartate; there is, in fact, a net flux of glutamate out of the fetus into the placenta. As both of these amino acids are major constituents of body proteins, the data indicate that they are formed within the fetus. The umbilical uptake of some neutral and basic amino acids (e.g., valine, leucine, isoleucine, arginine, phenylalanine, and tyrosine) is in considerable excess of estimated growth requirements, suggesting that some amino acids undergo extensive transamination and oxidative degradation in the fetus. Finally, the net uptake of nitrogen, carbon, and calories by the growing ovine fetus in the form of amino acids, glucose, and lactate is compared to estimated requirements as determined in previous studies.

Gestational changes in pulmonary vascular responses in fetal lambs in utero.

Abstract: Pulmonary arterial (PA) blood flow patterns, changes in pulmonary blood flow, and pulmonary vascular responses to graded hypoxemia and intravenous acetylcholine (ACh) were studied in 15 fetal lambs in utero 3-12 days after surgical implantation of an electromagnetic flow transducer and PA catheter Phasic PA flow in the fetus was forward only during the first third of systole, almost zero during midsystole, and backward during late systole and early diastole In contrast, neonatal lambs showed forward PA flow throughout systole The constriction of the fetal pulmonary vasculature in response to progressive hypoxemia varied with gestational age At 103 days there was no significant drop in PA flow and only a small increase in pulmonary vascular resistance (Rp) with hypoxemia The greatest increase in Rp was seen in fetuses after 121 days of gestation This response was unaffected by alpha- and beta-sympathetic and parasympathetic blockade Similarly, the pulmonary vascular response to ACh injected into the fetal jugular vein depended on gestational age Little or no increase in pulmonary flow was noted in the youngest fetus, whereas ACh produced a marked increase in pulmonary flow in festuses over 120 days of gestation These data suggest that the mechanisms by which hypoxemia constricts and ACh relaxes the pulmonary vascular smooth muscle are not fully developed in fetal lambs at 100 days of gestation and furthermore, that these mechanisms progressively develop during the last third of gestation

Effects of acetylsalicylic acid on the ductus arteriosus and circulation in fetal lambs in utero.

Abstract: Intra-arterial and intravenous catheters were inserted in six fetal lambs at 125-130 days of gestation. On the following day, fetal arterial pressures and blood gases were monitored and fetal cardiac output and its distribution were measured by injection of radionuclide-labeled microspheres 15 mum in diameter. Acetylsalicylic acid, 55-90 mg/kg of estimated fetal weight, then was administered into the fetal stomach. Fetal pulmonary arterial pressure rose significantly after an average of 58 minutes, increasing the pressure difference between the pulmonary artery and the aorta from 2 +/- 0.3 (SEM) mm Hg during control to 11.2 +/- 1.6 mm Hg. Resistance across the ductus arteriosus rose from 4.2 +/- 0.5 (SEM) to 27.4 +/- 4.01 units, and flow fell from 495 +/- 44 (SEM) to 409 +/- 20 ml/minute. The proportion of combined ventricular output distributed to the placenta, adrenals, heart, and lungs increased, whereas the proportion of combined ventricular output distributed to the brain, liver, intestine, kidneys, and upper and lower body fell. In two fetuses infusion of prostaglandin E1 reversed the pulmonary hypertension. Inhibition of prostaglandin synthesis in fetal lambs produced constriction of the ductus arteriosus and redistribution of cardiac output. It is probable that prostaglandins, particularly E1, are involved in regulation of blood flow through the ductus arteriosus and various vascular beds in the normal resting fetus.

Changes in levels of cellular retinol- and retinoic-acid-binding proteins of liver and lung during perinatal development of rat.

Abstract: Cellular retinol-binding protein and cellular retinoic-acid-binding protein, canditates for mediating the action of vitamin A, were found to be present in tissues of the fetal rat. Cellular retinol-binding proteins were still present in most tissues of the adult, but the retinoic-acid-binding protein was not detected in some, including lung, liver, intestine, and kidney. During perinatal development of lung the level of cellular retinol-binding protein remained relatively constant while the level of the cellular retinoic-acid-binding protein peaked at 10 days postnatally, then declined. It was not detectable in lung tissue from 21-day-old rats. In liver, however, the retinoic-acid-binding protein was not detectable later than 5 days postnatally, while the level of the cellular retinol-binding proteinrose sharply near birth, declining only after 21 days to the lower adult levels. The variations observed in the levels of the two binding proteins suggest different and changing requirements for retinol and retinoic acid in organ development and maturation.

Morphological development of the pulmonary vascular bed in fetal lambs.

Abstract: The morphological development that accompanies increasing pulmonary blood flow and decreasing pulmonary vascular resistance with advancing gestational age has not been delineated. To study this point we developed a method of comparing pulmonary arterial vessels of the same generations in fetal lambs. Pulmonary arteries were perfused with glutaraldehyde solution at pressures appropriate for gestational age and then injected with an India ink-gelatin-Micropaque mixture. Using the dissecting microscope and serially prepared sections we studied successively smaller generations of arteries. We assessed the medial width/external diameter ratio in a total of 825 vessels from six fetal lambs of 85 to 140 days gestation. In fifth generation, or resistance vessels, this ratio remained constant over the gestational period studied (N = 529, Y = 0.16, slope = 0.0003). We measured the volume of 17-34 randomly selected sections from each of the six fetuses, counted the total number of fifth and sixth generation vessels in these sections, and calculated the total number of these vessels per right lung. This number increased from 0.10 X 10(6) to 4.08 X 10(6) with increasing gestational age. The number of vessels per unit volume increased from 7.2 X 10(3)/ml to 61.8 X 10(3)/ml or right lung over this gestational period. The results indicate that increased pulmonary blood flow and decreased pulmonary vascular resistance with advancing gestation are due to an increase in the total number of vessels and increased vasomotor reactivity is related to an increase in the total amount of smooth muscle while the thickness of muscle in individual vessels remains constant.

Prenatal diagnosis of alpha-thalassemia. Clinical application of molecular hybridization.

Abstract: The technic of DNA-DNA hybridization was used for prenatal diagnosis of a pregnancy at risk for homozygous alpha-thalassemia. Fibroblasts were cultured from amniotic fluid, and the number of alpha-globin genes in the DNA was quantified by hybridization with radioactive DNA complementary to alpha-globin mRNA sequences. As compared to control studies of DNA from patients with alpha-thalassemia syndromes and from unaffected subjects, the results indicated that the fetus had alpha-thalassemia-1. The diagnosis was confirmed by umbilical-cord blood studies.

Development of Insulin and Glucagon Binding and the Adenylate Cyclase Response in Liver Membranes of the Prenatal, Postnatal, and Adult Rat: Evidence of Glucagon “Resistance”

Abstract: Although plasma glucagon levels in the rat fetus are in the adult range, hepatic glycogen is present in far greater abundance in the fetus than in the adult. To explain this paradox, adenylate cyclase response to glucagon was studied in partially purified membranes of rat livers obtained throughout perinatal life and at 3 months of age. The adenylate cyclase response to glucagon (10(-9) M) was only 7% of the adult response at day 15 of fetal life and 20% on the 21st day. No until after the 30th day postpartum did not reach maturity. Yet, the adenylate cyclase response to stimulation by NaF was comparable to the adult response throughout fetal life. The binding of [125I]iodoglucagon (2 X 10(-9) M) by these membrane preparations was only 1% of the adult level at day 15 of fetal life and increased to 23% at the 21st day, and, like the adenylate cyclase response to glucagon, did not reach maturity until after the 30th day of postnatal life. In contrast, insulin binding on the 15th day of gestation was 11% of the adult level and on the 21st day 45% of the adult level, reaching adult levels by the 30th postnatal day. An increase in membrane-associated particles, reflecting intramembranous protein, was observed during prenatal life, but the mean particle number per mum2 reached adult levels on the 21st day of fetal life, indicating that subsequent changes in hormone binding were clearly independent of non-specific changes in the number of particles. The findings suggest that the fetal liver is less sensitive to glucagon action than the adult liver, and that this glucagon "resistance" is mediated by a reduced capacity of the hepatocyte to bind glucagon at a time when substantial binding of insulin is demonstrable. Selective discrimination against glucagon may be important in promoting the anabolic processes required for normal fetal development.

Somatomedin-C receptor ontogeny and levels in porcine fetal and human cord serum.

Abstract: The ontogeny of somatomedin receptors in tissues of fetal pigs and levels of somatomedin- C in fetal pig serum at various gestational ages and in human cord serum was investigated. Specific binding of 125I somatomedin-C by particulate membranes prepared from fetal organs from a variety of gestational ages almost always exceeds specific I25I insulin binding. In liver, kidney, heart, and the maternal portion of the placenta, apparent binding affinity for somatomedin is relatively constant throughout gestation and is the same for membranes from fetal and adult animals. In contrast, in the fetal portion of the placenta, specific somatomedin-C binding and apparent binding affinity increases as gestation progresses. The changes in this tissue correlate temporally with the acceleration of growth of the pig fetus. Membranes prepared from fetal lungs exhibit higher specific binding of somatomedin and higher affinity constants than adult lung membranes. Somatomedin levels in fetal pig serum are about 25% of those o...

A membrane antigen common to human cancer and fetal brain tissues.

Abstract: Summary Membrane antigens of a cultured human melanoma line, UCLASO-M14, were studied using immune adherence techniques Allogeneic sera from melanoma patients that were reactive with the M14 but nonreactive with lymphoid cells of the M14 donor were used as antibodies The antigen responsible for the reaction between M14 and the antibodies was searched for in other cancer, normal, and fetal tissues using antibody absorption techniques The antigen was found in a variety of different histological types of biopsied and cultured cancer cells as well as in melanomas The antigen did not exist in biopsied normal tissues, but it appeared in cultured normal skin and muscle Neither normal lymphocytes nor cultured lymphoid cells showed any antigenicity The antigen was present in human fetal tissues and was the strongest in fetal brain tissues at 22 weeks of development Liver, Spleen, thymus, and small intestine from the same fetus were negative for antigen

Functional differentiation of the fetal anterior pituitary cells in the rat.

Abstract: The onset of hormone synthesis in the rat fetal pituitary gland was studied with the use of the peroxidase labelled antibody method. On the 16th day of fetal life, cells containing immunoreactive ACTH appeared in the primordial cell outgrowth of the Rathke's pouch. In some fetuses, also prolactin cells could be detected at the same developmental stage and these cells were present consistently on subsequent days. Differentiation of ACTH and prolactin cells was followed by onset of TSH, LH and GH synthesis on the 17th, 18th and 19th day of gestation, respectively.

Epizootic congenital arthrogryposis-hydranencephaly syndrome in cattle: Isolation of Akabane virus from affected fetuses

Abstract: Previous serological studies strongly suggested Akabane virus to be the etiologic agent of epizootic abortion and congenital arthrogryposis-hydranencephaly in cattle, and this view was further corroborated in this study by the isolation of the virus from an aborted fetus in an epizootic of the disease and from a fetus extracted from a cow which was suggested by serologic tests to have a recent infection with the virus. The latter fetus had histological changes of encephalomyelitis and polymyositis, and specific antigens of Akabane virus was shown by the immunofluorescent technique in brain tissues as well as skeletal muscular tissues. The virus was recovered from various fetal tissues and fluids, and in relatively large amounts from brain, spinal cord, cerebral fluid, skeletal muscles and fetal placenta. The intracranial inoculation of suckling mice, 1–2 days of age, was the most sensitive system for Akabane virus isolation and Hm Lu-1, a continuous cell line from hamster lung, seemed almost as sensitive as suckling mice.

Some aspects of foetal and uteroplacental metabolism in cows with indwelling umbilical and uterine vascular catheters.

Abstract: 1. 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. Rountine 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 O2, 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/O2 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 and the metabolic activity of the uterine tissues are discussed in relation to comparable findings in the sheep.

Prenatal diagnosis of genetic disorders.

Abstract: Three hundred and fifty pregnancies were monitored by transabdominal amniocentesis in the fourteenth to sixteenth week of gestation followed by karyotyping or biochemica assays of cultured amniotic fluid cells and analysis of alpha-fetoprotein in the amniotic fluid supernatant. The pregnancy was interrupted in 36 cases (10%) either becasue of a fetal abnormality or the presence of a male fetus in pregnancies at risk for an X-linked disease. Four chromosomal aberrations were found in 87 pregnancies tested because of advanced maternal age. In 101 pregnancies with a recurrence risk of Down's syndrome, 2 fetuses with an abnormal karyotype were detected. In 11 cases, in which 1 parent was a carrier of a balanced translocation, 2 unbalanced fetal karyotypes were found. Fetal chromosome studies in 43 pregancies at risk for an X-linked disease indicated the presence of a male fetus in 21 cases. Prenatal diagnosis of 11 different metabolic diseases was performed in a total of 34 cases. Microchemical techniques were used to allow completion of the diagnosis of seven different enzyme deficiencies within 9 to 22 days after amniocentesis. Alpha-fetoprotein assay in the amniotic fluid supernatant of 47 pregnancies at risk for an open neural tube defect resulted in the detection of 3 anencephalic fetuses during the second half of pregnancy. The safety and reliability of amniocentesis and the possible effects on the outcome of pregnancy are evaluated. Prenatal diagnosis offers a promising alternative for parents who are at risk of having a child with a genetic disease which can be detected in amniotic fluid or in cultured amniotic fluid cells.

The fate of diethylstilbestrol in the pregnant mouse.

Abstract: There is much current interest in the effect of diethylstilbestrol (DES) on the mammalian fetus; however, little is known concerning the physiologic disposition of DES during pregnancy. Radiolabeled (14C or 3H) DES (30 mug/kg) was given to 16-day pregnant mice and its metabolism, distribution and excretion were studied. After i.v. administration, DES was rapidly cleared from the plasma. The plasma decay rates could be described by the sum of four exponentials having T 1/2 values of 4 seconds, 1.1 minutes, 14 minutes and 13 hours. Moreover, conjugated products of DES accounted for more than one-half of the plasma radioactivity by 5 minutes after dosing. The parent compound was rapidly distributed to blood cells, but the liver was the major site of accumulation of DES and its metabolites. In fact, the total radioactivity in this organ accounted for 50% of the injected dose within 2.5 minutes after treatment. Significant concentrations of radioactivity persisted in liver throughout the 16-hour experiment, with DES conjugates accounting for 80% of the hepatic 14C activity at all time points examined. Approximately 56% of the dose was excreted in the feces within 24 hours, primarily as the parent compound. With DES as substrate, significant levels of UDP-glucuronyltransferase were determined in maternal and fetal liver but not in maternal uterus, placenta of fetal gut. Although the mouse placenta appeared to retard the passage of DES into the fetal compartment, a 3-fold accumulation (relative to fetal plasma) of the compound was found in the fetal reproductive tract.

Human pancreatic islets in culture: effects of supplementing the medium with homologous and heterologous serum

Abstract: Islets of Langerhans, isolated from the human fetal pancreas and cultured in media supplemented with serums from human umbilical cord or adult donors, remained intact, free-floating, and functional for 2 to 5 months. Substitution of fetal calf serum for the human serum usually resulted in attachment of islets, monolayer formation, and relatively early (3 weeks) functional arrest.

Free and Conjugated Steroids in Maternal and Fetal Plasma in the Cow Near Term

Abstract: Plasma samples were collectedin 5 pregnant cosa (between Days 247 and 273 postconception) via indwelling cathetersfrom the maternal jugular and uterine veins, umbilicalarteryand vein and the fetalvena cava caudalis.Four fetusesdied within four days and the fifthwas born aliveon Day 3 postsurgery. Progesterone (P),Testosterone (T) as wellas freeand conjugated (enzyme hydroly- sis)cortisol(F), corticosterone (B), estrone (E5), estradiol-17oand -17� (E20, E2�) were deter- mined by CPB and RIA respectively. Steroid concentrations showed a distinct separation between maternal and fetal circulation. Fetal P was low (� = 0.20 ng/ml) but maternal P was high as antici- pated for the stage of pregnancy, while T values were low in all sampling sites (0.08 - 0.55 ng/ml). Corticoids were higher in the maternal than fetal compartment except in one cow which was cannulated post Day 270 where F increased in the fetus within 4 days from 71 to 102 ng/ml on the day of parturition. No significant changes in F/B-ratios occurred in maternal samples while fetal plasma F/B ratios increased during the sampling period. Conjugated F and B were 5 percent and 10 - 20 percent of the free, respectively, while conjugated estrogens could exceed the free estro- gens by a factor of 10 to 100 reaching concentrations above 100 ng E20/ml in 2 samples in the fetus. Free and conjugated E1 was the major maternal estrogen while it was Esa in the fetus. In both compartments lowest concentrations were found for E2p (free: 0.007 - 0.060 ng/ml, con- jugated 0.04 - 1.69 ng/ml, depending on the sampling site). Except for E2p and based on paired samples, estrogen levels in the uterine vein were higher than in the jugular vein, and in the fetus they were highest in the vena cava and lowest in the umbilical artery.

Relationships between pressure and flow in the umbilical and uterine circulations of the sheep.

Abstract: We studied the relationship of fetal and maternal vascular pressures to umbilical and uterine blood flow in the unanesthetized ewe and in the sheep fetus in utero by placing electromagnetic flow transducers around both the common umbilical and uterine arteries. Reductions in umbilical arterial pressure or elevations in umbilical venous pressure decreased umbilical blood flow without affecting either the uterine arterial blood flow or other maternal cardiovascular variables which were studied. Elevations in uterine venous pressure or reductions in uterine arterial pressure decreased uterine arterial flow but these interventions had no effect on umbilical blood flow until fetal hypoxemia and bradycardia occurred. When the bradycardia of the fetal hypoxic response was inhibited by atropine, alterations in maternal vascular pressure had no effect on umbilical arterial flow. These data do not support the presence of a "sluice" or "waterfall" effect in the umbilical-placental circulation of the sheep fetus in utero.

The production of Mullerian inhibiting substance by the fetal, neonatal and adult rat.

Abstract: The intensity and duration of Mullerian Inhibiting Substance (MIS) secretion by the fetal newborn and adult rat testes and the effect of the placenta and pituitary on the secretory pattern was studied in vivo and in vitro. A graded organ culture assay was used to determine the secretory pattern. Production of MIS was evident during the last trimester of pregnancy. MIS production continued during the 1st 3 weeks of neonatal life and then disappeared around the time of weaning. Hypophysectomy performed at 20 days of age failed to restore MIS activity in adult animals. Fragments of placenta in testis culture did not influence MIS activity in perinatal testes. MIS exhibited a regressive effect on Mullerian ducts placed at a distance from a testicular source.

Studies on the equine placenta II. Ultrastructure of the placental barrier.

Abstract: In early pregnancy the equine placenta consists of a simple apposition of fetal and maternal epithelia, but it becomes more complex with the formation of microcotyledons between 75 and 100 days of gestation. Although the placental barrier maintains an epitheliochorial arrangement throughout the course of pregnancy, a thinning of the maternal epithelium and a progressive indentation of the chorionic epithelium by fetal capillaries shortens the length of the diffusion pathway and reduces the amount of placental tissue between fetal and maternal bloodstreams. These structural modifications may reflect the changing requirements of the fetus for O2 and other metabolites as gestation proceeds. During the first 200 days of pregnancy there is evidence of intense pinocytotic activity by the cells of the trophoblast. From the 100th day of pregnancy there is a pronounced development of smooth endoplasmic reticulum, while rough endoplasmic reticulum and irregular, dense, membrane-bound bodies are a prominent feature of the paranuclear cytoplasm from Day 200. These changes suggest that the cells of the trophoblast become more highly involved in synthetic processes with increasing gestational age.