Showing papers on "Fetus published in 1985"

Extent of nicotine and cotinine transfer to the human fetus, placenta and amniotic fluid of smoking mothers

Abstract: Nicotine and cotinine concentrations were measured in placental tissue during the first trimester, in amniotic fluid during the second trimester and in placental tissue and fetal serum at birth. These values were compared to the corresponding serum concentrations of the smoking mothers. Nicotine concentrations in the placentas (range 3.3-28 ng/g), in amniotic fluid (range 1.5-23 ng/ml) and in fetal serum (range 0.5-25 ng/ml) were all higher than the corresponding maternal serum values: amniotic fluid/maternal vein serum concentration ratio 1.54 +/- (SD) 0.27 (n = 23; week 16-24 of gestation), umbilical vein serum/maternal vein serum ratio 1.12 +/- 0.30 (n = 26; at birth); placental tissue/maternal vein serum ratio 2.58 +/- 1.30 (n = 17; at birth); these ratios were between 1.2 and 5 during week 10 of gestation (n = 3). The ratios did not depend on the time between the last cigarette smoked and sampling. Significant correlations were found between nicotine concentrations in amniotic fluid and maternal serum (r = 0.88), between fetal and maternal serum levels (r = 0.88) and between placental and maternal serum levels (r = 0.52). Cotinine concentrations in placental tissue (range 10-131 ng/g), amniotic fluid (range 5-188 ng/ml) and fetal serum (range 15-233 ng/ml) were lower than or similar to corresponding maternal serum levels. Our results indicate that the human fetus is exposed to higher nicotine concentrations that the smoking mothers.

Effects of maternal hypothyroidism on the weight and thyroid hormone content of rat embryonic tissues, before and after onset of fetal thyroid function.

Abstract: Embryonic tissues were obtained from normal (C) and thyroidectomized (T) rats between 9 and 21 days of pregnancy. We determined the number and weight, as well as the T4 and T3 contents (RIA), of 9- to 12-day-old embryotrophoblasts, of 13- to 21-day-old embryos and placentas, and of liver, lung, and brain from 20- and 21-day-old fetuses. T4 and T3 were found in all samples obtained from C dams, both before and after onset of fetal thyroid function. Despite low levels of both iodothyronines in fetal plasma near term, their concentrations in fetal brain and lung had reached half the maternal values. The T3/T4 ratio in fetal organs was the same, or higher, than in adult rats. Maternal thyroidectomy resulted in a marked decrease of the number and individual weights of viable conceptuses, throughout gestation. Fetal organ weights near term were also decreased, and changes were found in brain DNA and protein concentrations. T4 and T3 were undetectable in all embryotrophoblasts, embryos and placentas obtained fro...

The early ontogenesis of thyroid hormone receptor in the rat fetus.

Abstract: We have determined the concentration of thyroid hormone receptor binding sites in nuclear extracts derived from rat fetal organs throughout gestation and the postnatal period. Before day 14 of gestation nuclear extracts were obtained from whole fetuses. No receptor binding activity could be detected at day 12 of gestational age, and small amounts were detected at day 13 (maximum binding capacity less than 50 fmol/mg DNA). The receptor could be measured in pools of individual organs from day 14 (brain) or from day 16 (heart, liver, and lung) onwards. The order of analog binding affinity at 14 days was triiodothyroacetic acid = T3 greater than T4 greater than rT3, suggesting that at 14 days of fetal age the receptor has the same binding specificity as the receptor from mature tissues. In brain, the concentration of binding sites increased from 77 fmol/mg DNA at 14 days to 210 fmol/mg DNA at 17 days, remaining at this level until birth. Receptor concentration was identical whether the binding assays were performed on purified nuclei or nuclear extracts. There was no effect of maternofetal hypothyroidism on receptor concentration in the brain at 21 days of gestational age. Lung concentrations of receptor also remained constant during the fetal period. During the postnatal period, there was an increase in receptor concentration in brain and lung, with maximum levels at day 6. The pattern of receptor development in heart and liver was different, since its concentration increased progressively throughout the fetal and postnatal periods towards the levels found in adult rat tissues. The results suggest that the appearance of the thyroid hormone receptor coincides with that of the first fetal thyroid gland structures, but that it occurs much before thyroid function is fully established. As far as the receptor is concerned, fetal tissues have the potential to respond to thyroid hormone as early as the 13th day of gestational age.

Delay in the fetal globin switch in infants of diabetic mothers.

Abstract: In the normal fetus, a switch from production of hemoglobin F (alpha 2 gamma 2) to hemoglobin A (alpha 2 beta 2) occurs at 28 to 34 weeks of gestation. In the fetus with beta-hemoglobinopathy or beta-thalassemia, this switch proceeds despite the morbidity that results when production of beta-globin is abnormal or reduced. Since insulin has recently been shown to induce renewed expression of some inactive genes, we studied globin biosynthesis during the natural evolution of the fetal globin switch under conditions of hyperinsulinemia, which occurs in infants of diabetic mothers. Such infants develop in a hyperglycemic environment, which produces reactive hyperinsulinemia. The normal increase in beta-globin production from pre-switch levels did not occur in 9 of 10 such infants at term, as compared with 11 normal infants, in whom the switch occurred by 36 to 39 weeks of gestation (P less than 0.0001). The delay in the switch from gamma-globin to beta-globin in this unique clinical setting may allow identification of physiologic factors that can modulate developmental gene suppression.

Essential fatty acids interconversion in the human fetal liver.

Abstract: In order to study the role played by the fetoplacental unit in providing the human fetus with arachidonic acid, delta 5- and delta 6-desaturase activities were studied in microsomes from human fetal liver and placenta after 18 and 22 weeks of gestation We evidenced for the first time delta 5- and delta 6-desaturase activities in fetal liver microsomes As in adult liver, delta 6-desaturation is the rate-limiting step of arachidonic acid synthesis No activity was found in the placenta Arachidonic acid concentrations were higher in fetal serum than in maternal serum while the opposite was observed for linoleic acid The fetal liver microsomal content in arachidonic acid was low Taken together the data suggest that arachidonic acid is supplied to the fetus through a preferential transfer across the placenta

Maternal and fetal responses to exercise during pregnancy

Abstract: Exercise has numerous effects on the pregnant woman, the developing fetus, and the placenta. In turn, pregnancy affects the ability to perform physical activity. During pregnancy, increased metabolism at rest results almost exclusively from the gestational increase in mass. Because of this increase, a higher cardiorespiratory effort is required to perform a given amount of external work. One would expect the result to be some training effect, unless a more sedentary lifestyle is adopted. The possibility that maximal O2 consumption may increase during pregnancy has not been studied extensively, yet it is a most important variable that puts other changes in perspective. The sedentary lifestyle commonly adopted in late pregnancy in most western societies may reflect a cultural rather than a physiological phenomenon. In contrast to the physiological alterations in the mother and despite the reductions in uterine blood flow during maternal exercise, physiological changes in the fetus are small. Relatively minor changes occur in the blood concentrations of O2 and substrates during prolonged exhaustive exercise. In addition, despite a temperature increase of 1 to 2 degrees C, there is little evidence for significant alteration in fetal metabolism, cardiovascular hemodynamics, or blood catecholamine concentrations. These observations suggest that acute exercise normally does not represent a major stress for the fetus. Of course, most of the information concerning the fetus is derived from studies in experimental animals, particularly in sheep. In humans the upright position and increased uterine contractibility may affect the fetal responses differently. Virtually nothing is known about the physiological effects of exercise training on the fetus. The most likely effect may be a relatively small reduction in birth weight in some species, but this needs further investigation. Further studies are also needed for a more complete understanding of the mechanisms involved in the remarkably effective mechanisms that account for the relative homeostasis of the fetus during maternal exercise.

Ontogeny of Hypothalamic Luteinizing Hormone- Releasing Hormone (GnRH) and Pituitary GnRH Receptors in Fetal and Neonatal Rats*

Abstract: Although it is known that LH secretion starts at 17 days of gestation in the fetal rat and that this first LH release is most likely driven by hypothalamic GnRH, an earlier role for GnRH during fetal life has been postulated with the observation that presence of GnRH is important before day 13 of gestation for the differentiation of the pituitary anlage. In order to clarify the different roles of GnRH during fetal life, we have studied the first appearance of GnRH in the fetal brain, the expression of GnRH receptors in the fetal pituitary gland, and the presence of GnRH immunoreactivity within the fetal gonadotrophs. GnRH was present in the earliest brain tissue examined (12 days of gestation). From 12–17 days, GnRH content of fetal brain remained low and then increased markedly by the end of gestation. No immunoreactive GriRH-like material could be detected in rat placental tissue throughout gestation. Binding sites for GnRH were detected as early as 12 days of gestation in fetal pituitary glands. Howeve...

Dexamethasone Stimulation of Fetal Rat Lung Antioxidant Enzyme Activity in Parallel With Surfactant Stimulation

Abstract: It has recently been determined that fetal lung antioxidant enzyme activity markedly increases late in gestation. A test was made of whether this normal late-in-gestation change in O2-protective enzymes would be responsive to the maturing effect of hormonal (glucocorticoid) treatment. Pregnant rats received 0.2 mg/kg of dexamethasone (or saline) at 48 and 24 hours prior to delivery of their fetuses on gestational days 19, 20, 21, and 22 (newborn). Lung disaturated phosphatidylcholine showed an expected response to prenatal dexamethasone exposure with significant elevations of surfactant lipid at gestational days 20 and 21. A similar effect of prenatal dexamethasone treatment on the lung antioxidant defensive system was found. Superoxide dismutase, catalase, and glutathione peroxidase--enzymes protective against hyperoxia-induced lung injury--showed an accelerated pattern of maturation with significant increases in the dexamethasone-treated fetal lungs compared with control fetal lung enzyme levels at gestational days 20 and 21. The results suggest that prenatal dexamethasone treatment may have dual benefits when used in impending premature deliveries--that is, it may stimulate maturation of both the surfactant system and also the antioxidant enzyme system, and this maturation can help protect the premature newborn's lungs from the toxic complications of hyperoxic therapy that may be required because of immaturity.

The placenta as a site of cytomegalovirus infection in guinea pigs.

Abstract: The development of cytomegalovirus (CMV) infection in the placenta was studied in Hartley guinea pigs inoculated at midgestation, and its role in determining the outcome of fetal CMV infection was assessed. A hematogenous spread of CMV from the mother to the placenta occurred early during the course of the infection. However, the virus remained present in placental tissues long after CMV had been cleared from maternal blood (i.e., 3 and 4 weeks postinoculation). At that time, the virus was able to replicate in placental tissues in the presence of specific maternal antibodies. Viral nucleocapsids were seen within nuclei of trophoblastic cells, and virions were present surrounding infected cells. In addition, typical CMV-induced histopathological lesions bearing CMV antigens were consistently localized at the transitional zone between the capillarized labyrinth and the noncapillarized interlobium. Whenever CMV infection of the fetus occurred, virus was isolated from the associated placenta. Among placental-fetal units with CMV-infected placentas, only 27% of the fetuses were found to be infected. In addition, there was a delay in the establishment of the infection in the fetus in relation to the placenta, although frequencies of virus isolation in placental and fetal tissues peaked at 3 weeks after CMV inoculation. These results suggest that during primary CMV infection of pregnant guinea pigs, the placenta not only serves as a reservoir for CMV but also acts to limit transmission of the virus to the fetus.

Fetal lung development in the diabetic pregnancy.

Abstract: It seems quite likely that the normal process of fetal lung biochemical maturation is delayed by maternal diabetes and that abnormalities in the pulmonary surfactant system are involved. The appearance of PG in amniotic fluid and possibly in fetal lung is impaired or at least delayed. The same is possibly true for DSPC, the main constituent of surfactant, but recent discrepant data call for further clarification of this specific point. Careful determination of the fetal lung phospholipid profile by amniotic fluid analysis helps predict and prevent RDS in IDM, along with a careful control of the maternal diabetic condition. A study of alveolar surfactant at birth, if it could be performed in addition to amniotic fluid analysis, would help to better characterize surfactant deficiency in IDM. On the basis of both in vivo and in vitro experimental approaches, it seems clear that hyperglycemia and fetal reactional hyperinsulinism are both involved in the processes delaying fetal lung maturation. Further advances in the understanding of cellular and molecular mechanisms leading to this delay will be conditional on the availability of animal models reproducing the features of the metabolic and hormonal environment of human fetuses in diabetic pregnancies. The appropriateness of in vivo models needs to be defined by two kinds of criteria: 1) presence of simultaneous hyperglycemia and hyperinsulinemia in the fetus; 2) the presence of delayed fetal lung maturation as judged by morphology and morphometry of epithelial lung cells, by physiological assessment of surfactant, and by the phospholipid composition of the lung (and including lung tissue per se, bronchoalveolar lavage fluid, lamellar bodies, and/or isolated surfactant fractions). Therefore, future studies must necessarily be comprehensive in scope and include information indicating that fetal growth, blood glucose, and circulating insulin are all increased. Such models already exist in rats and rabbits. Rat models are possibly not the best because of the high basal level of fetal blood insulin in this species and the relatively rapid rate of lung maturation that is not analogous to the human. Monkey models are of interest, because of their close relationship with the human pregnancy, and need to be studied further. They are particularly attractive also because primary fetal hyperinsulinism can be studied (268), as well as the combination of hyperglycemia and hyperinsulinemia in pregnancies of STZ-treated monkeys (152). An appropriate model of the diabetic pregnancy could provide answers to the following questions. Are the biosynthetic pathways of surfactant phospholipids directly impaired?(ABSTRACT TRUNCATED AT 400 WORDS)

Viral diseases of the fetus and newborn

Abstract: Both authors are eminent workers in microbiology and both are also active in clinical practice and have contributed extensively from both the laboratory and the bedside. The more extensive chapters are those dealing with rubella by Professor Dudgeon from London, who explores all aspects including mass immunization and the late handicaps which are often insufficiently appreciated, and the chapter on congenital cytomegalovirus wherc many extensive studies are integrated by Dr. Hanshaw who has himself contributed so much to this. Other chapters deal with the growing problem, especially in America, of herpes simplex, and with infections by the enteroviruses, and with varicella-zoster, smallpox and vaccinia, hepatitis and other agents. Valuable chapters on the pathology of the placenta and on the development of immune mechanisms are contributed by W. A. Blanc and by W. C. Marshall.

Normal reference ranges for biochemical substances relating to renal, hepatic, and bone function in fetal and maternal plasma throughout pregnancy.

Abstract: Normal reference ranges for sodium, potassium, urea, creatinine, calcium, phosphate, total protein, albumin, bilirubin, alkaline phosphatase, and aspartate transaminase were determined from 344 fetal and maternal plasma samples between 15 and 38 weeks' gestation. Pure fetal blood was obtained by fetoscopy in the second trimester and in the third trimester by umbilical cord puncture at delivery. All biochemical substances were measured by continuous flow (SMAC, Technicon) except albumin, which was measured by turbidimetry (CobasBio, Roche). The resulting data were analysed on an AMDAHL 470A computer and reference ranges covering 2.5 to 97.5 percentiles were defined. Analysis of variance was performed to examine the overall effect of gestational age on the analytes measured and on the changes in the fetal compartment relative to the mothers'. A paired t test was performed to examine how these biochemical substances in fetal plasma related to maternal plasma from the same pregnancy.

Metabolic and cardiovascular effects on fetal sheep of sustained reduction of uterine blood flow.

Abstract: The effects on the fetus and placenta of graded reductions of uterine blood flow to 30-90% of control have been studied in sheep at days 125-143 of pregnancy. Reduction of uterine flow to 70-90% of control had little effect upon fetal oxygenation or heart rate or blood pressure but elevated fetal plasma catecholamine concentration. Reduction of flow to 30-50% of control depressed fetal arterial and umbilical venous PO2 but had little effect upon oxygen consumption unless the umbilical venous value fell below about 14 mmHg when it was depressed by up to 30%. Placental oxygen consumption did not fall and was therefore maintained at the expense of the fetus. Fetal arterial pressure rose by 10-12 mmHg and heart rate fell by about 30 beats/min during the first 10-15 min then rose above its initial value. Plasma adrenaline and noradrenaline concentrations rose progressively at a rate which increased with greater degrees of asphyxia. When uterine blood flow was reduced below one-half of normal, net placental consumption of glucose fell and there was evidence of substantial provision of glucose and lactate from the fetus. Fetal production of lactate increased sharply and much of this appeared to be consumed by the placenta at a rate sufficient to account entirely for the deficit in net glucose consumption. The results are consistent with the hypothesis that the fetus senses even small changes in uterine blood flow that are alone insufficient to elicit significant blood gas changes. When the fall in uterine flow caused by arterial compression is relatively large, nutrient supply to the placenta is maintained at the expense of the fetus and as a result of fetal glucose and lactate production. The elevation of fetal arterial PCO2 appears to enhance fetal responses to hypoxia. The results are discussed in relation to the fetal responses to brief and prolonged reductions in uterine blood flow.

Effects of chronic environmental heat stress on blood flow and nutrient uptake of the gravid bovine uterus and foetus

Abstract: To evaluate the effects of chronic environmental heat stress during mid-gestation on gravid uterine and foetal metabolism, mature Hereford cows were assigned to control (n = 8) or heat stress (n = 5) treatments beginning on day 100 of gestation. Uterine and umbilical blood flows were estimated by the steady-state diffusion procedure on day 169 ± 4 of gestation. Oxygen (O2), glucose, lactate, α-amino nitrogen and urea nitrogen concentrations were determined for uterine and umbilical blood samples collected during this procedure. Foetuses and foetal fluids were collected on day 174±4.Uterine and umbilical blood flows were reduced and foetal weight also was less for heat-stressed than for control cows. In addition, foetal liver weight as a proportion of foetal weight and total foetal liver RNA and protein were less for heat-stressed cows. Uterine and umbilical arterial–venous concentration differences in metabolites were similar between the two groups. Uterine, foetal and utero-placental uptake or secretion rates of the metabolites measured in this study were reduced in the heat-stressed cows, primarily because of differences in blood flow. Thus, chronic heat stress during mid-gestation had an adverse effect on foetal development resulting, at least in part, from decreased uterine and umbilical blood flows, which led to a reduction in uterine, utero-placental and foetal nutrient uptake or secretion rates.

Testosterone levels in midtrimester maternal and fetal plasma and amniotic fluid

Abstract: Testosterone was measured in maternal plasma (58 samples), amniotic fluid (71 samples) and fetal plasma (55 samples) in 79 patients between 15 and 23 weeks' gestation. Maternal plasma testosterone levels were unrelated to fetal sex. Amniotic fluid testosterone was significantly higher in male than female fetuses but did not reliably predict fetal sex. A correct diagnosis of fetal sex was made by testosterone assay of pure fetal plasma in 39 out of 40 males and in 15 out of 15 females using 1.70 nmol/l as the cut-off value. This investigation is not the method of choice for routine fetal sexing but may be of value in fetuses suspected of having certain endocrine disorders.

Plasma oxytocin in human pregnancy and parturition

Abstract: Oxytocin concentrations were determined in serial peripheral plasma samples collected from clinically normal women during pregnancy and labor. Measurable concentrations of this hormone were detected in all maternal plasma samples during pregnancy, but there were wide differences in values between patients. Serial samples from individual patients revealed a pattern of gradual rise of oxytocin levels with advancing gestation and the increase in concentration was statistically significant. There were no significant differences in oxytocin levels at any stage of labor, with or without epidural analgesia. Oxytocin levels at the onset of the second stage did not differ statistically from those at crowning. Comparison of cross-sectional data showed no significant difference between the mean oxytocin concentration in early labor and in late pregnancy. Oxytocin surges occurred, but not in a regular pattern. Plasma oxytocin concentration did not increase after pelvic examination, sweeping of the membranes, low amniotomy or after cervical vibration. After spontaneous vaginal delivery, umbilical arterial plasma levels of oxytocin were consistently higher than plasma concentrations from the umbilical vein. The fetal arterio-venous difference was less pronounced at elective cesarean section. At spontaneous vaginal delivery, with and without epidural anesthesia, plasma levels from the umbilical artery were significantly higher than the maternal levels. After vaginal delivery, oxytocin levels in cord plasma were significantly higher than at elective abdominal delivery. Some methodological aspects with regard to blood sampling and to plasma oxytocin radioimmunoassay procedures are discussed. From the results presented it is concluded that the human fetus can be an important source of oxytocin and that neurohumoral birth reflexes described in animals do not occur systematically in man.

Umbilical Velocity Wave Ratios in Human Pregnancy

Abstract: Umbilical artery velocity waves were measured in the fetuses from 130 pregnant women. One hundred eighty-five determinations were carried out from the fourteenth to the fortieth weeks of pregnancy. Detection of waveforms was carried out on an Angioscan Doppler spectrum analyzer. The umbilical artery velocity waves can be differentiated from other fetal signals by recognition of the pattern. The systolic peak of the velocity wave was divided by the end-diastolic value, thereby giving an S/D ratio. The use of a ratio overcomes the obstacle of not knowing the angle between the incident beam and the direction of motion. The umbilical velocity wave S/D ratio in normal pregnancies declines from 2.8 to 2.2 from 25 to 41 weeks. In pregnancies which result in a small-for-gestational age (SGA) fetus, the ratio is significantly higher, showing an average level of 3.8 at 29 weeks and declining to 3.0 at 40 weeks. Abnormal umbilical velocity wave values are seen in an SGA fetus, unexplained fetal death, poorly controlled diabetes mellitus, and a twin transfusion syndrome. Application of this technique has the potential of being an important aid in prenatal care.

Leukotriene end organ antagonists increase pulmonary blood flow in fetal lambs.

Abstract: The factors responsible for maintaining the normally low pulmonary blood flow and high pulmonary vascular resistance in the fetus are not well understood. Since leukotrienes are potent pulmonary vasoconstrictors in many adult animal species, we determined whether leukotrienes were perhaps involved in the control of the fetal pulmonary circulation by studying the effects of putative leukotriene end organ antagonists in two groups of fetal lambs. In six fetal lambs studied at 130-134 days gestation, FPL 55712 increased pulmonary blood flow by 61% (P less than 0.05) and reduced pulmonary vascular resistance by 45% (P less than 0.05). There was a small increase in heart rate but no changes in pulmonary and systemic arterial pressures and systemic arterial blood gases. In six other fetal lambs studied at 130-140 days gestation, FPL 57231 increased pulmonary blood flow by 580% (P less than 0.05) and decreased pulmonary vascular resistance by 87% (P less than 0.05). Pulmonary and systemic arterial pressures decreased (P less than 0.05), and heart rate increased (P less than 0.05). Leukotriene end organ antagonism significantly increases fetal pulmonary blood flow and decreases pulmonary vascular resistance. Leukotrienes may play a role in the physiological control of the fetal pulmonary circulation.