Showing papers on "Fetus published in 1986"

Pathology of the placenta.

Abstract: The placenta has a considerable functional reserve capacity, easily repairs ischaemic damage, is able to compensate for toxic injury and does not appear to age. Most of the macroscopically visible abnormalities of the placenta are of no functional significance, the major exception to this general banality being the uncommon large haemangioma which can cause complications in the mother, fetus and neonate. Most of the histological abnormalities seen in the placental villi represent a reaction to alterations in either maternal or fetal blood flow through the placenta, but a failure of adequate maturation of the villous tree may impair the functional efficiency of the placenta, as may defective trophoblastic differentiation. Infections of the placenta are important but do not influence placental function, whilst there is currently no firm evidence that the placenta ever suffers immune-mediated damage. Intrinsic placental 'insufficiency' is extremely rare and it is becoming increasingly clear that this clinical syndrome is usually due to a restricted supply of maternal oxygen and nutrients as a result of inadequate transformation of the spiral arteries into uteroplacental vessels. This failure of placentation represents an abnormality of the relationship between fetal and maternal tissues at a relatively early stage of pregnancy, and it is only by gaining a better understanding of this relationship that the problems posed by such conditions as pre-eclampsia and idiopathic intrauterine growth retardation will be answered.

High levels of corticotropin-releasing hormone immunoactivity in maternal and fetal plasma during pregnancy.

Abstract: Corticotropin-releasing hormone immunoactivity (CRHi) was measured in the plasma of 31 pregnant women and 6 nonpregnant women as well as in the umbilical cord plasma of 40 term fetuses. CRHi was not detectable (>44 pg/ ml) in the plasma of 6 nonpregnant women or in 6 women in the first trimester of pregnancy. Mean plasma CRHi rose progressively to 58 † 18 and 270 † 68 pg/ml during the second and third trimesters, respectively, and again became undetectable within 24 h after delivery. Mean CRHi in 40 umbilical cord plasma samples was 136 † 16 pg/ml. Gel filtration of both fetal and maternal plasma showed that the majority of the CRHi eluted in the same position as synthetic human CRH. There was no significant correlation between CRHi and either /8-endorphin or ACTH in umbilical cord plasma, suggesting that this CRHi may not be primarily responsible for the release of β-endorphin and ACTH into fetal plasma at delivery. A close correlation (r = 0.82) was found between simultaneously obtained maternal and umb...

Effect of gestational age on fetal and intervillous blood gas and acid-base values in human pregnancy.

Abstract: Intervillous, umbilical venous and umbilical arterial blood samples were obtained by cordocentesis or fetoscopically from 200 pregnancies at 16–38 weeks gestation. The fetuses were either not affected

Hematological Values of 163 Normal Fetuses between 18 and 30 Weeks of Gestation

Abstract: Utilizing an easy and safe procedure for fetal blood sampling in utero we have studied 409 fetuses for prenatal diagnosis of rubella, toxoplasmosis, hemophilia, and hemoglobinopathies. Retrospectively we selected 163 fetuses confirmed as normal at birth and tested between 18 and 30 wk of gestation to establish normal hematological parameters and to follow the evolution of erythropoiesis, differential counts, hemoglobin synthesis, and hemostasis. Total white blood cell and platelet counts did not change during this period. The lymphocytes represented the main population and we observed a decrease of normoblasts during gestation. The results show a progressive increase of red blood cells and hemoglobin. This evolution is demonstrated by the ratio hemoglobin A to acetylated hemoglobin F. No significant modification of hemostasis was observed over a 12-wk intrauterine gestation. These results provide useful reference values for future investigations.

Maternal Antibodies against Fetal Cardiac Antigens in Congenital Complete Heart Block

Abstract: An immunologic basis for congenital heart block has been proposed previously. To investigate the association between congenital heart block and maternal antibodies capable of crossing the placenta, we used immunofluorescence to examine serum samples from 41 mothers and 8 affected children, together with serum from controls, for antibodies to fetal cardiac tissue. Twenty-one mothers (51 percent) had IgG antibody reactive with fetal heart tissue, as compared with only 9 of 94 controls (10 percent; P less than 0.001). Three of 8 affected babies, but none of 50 healthy babies, had similar antibodies. The antibodies reacted with all myocardial tissue and were not directed specifically to the conduction system. They also reacted with other fetal tissues and could be distinguished from nuclear and smooth-muscle autoantibodies. We also observed a higher occurrence of antibodies to cytomegalovirus, but not to Epstein-Barr virus, in these mothers. Autopsy specimens from babies with congenital heart block examined by immunoperoxidase staining showed deposition of immunoglobulin and complement components in all cardiac tissues. These findings strengthen the case implicating immune reactivity related to maternal antibody in the development of some but not all cases of congenital heart block.

Developmental expression of genes for the stereoidogenic enzymes P450scc (20,22-desmolase), P450c17 (17 alpha-hydroxylase/17,20-lyase), and P450c21 (21-hydroxylase) in the human fetus

Abstract: Fetal adrenal steroidogenesis is required for the production of placental estrogen, and fetal testicular steroidogenesis is required for the development of male external genitalia. We studied the ontogeny and tissue specificity of expression of the genes for three steroidogenic enzymes: P450scc (the cholesterol side-chain cleavage enzyme), P450c17 (17 alpha-hydroxylase/17,20-lyase), and P450c21 (21-hydroxylase) in the human fetus. RNA from fetal tissues was probed with homologous human P450scc, P450c17, and P450c21 cDNAs cloned in our laboratory. At 20-21 weeks gestation, P450scc mRNA was most abundant in the adrenal, followed by testis, placenta, and ovary. P450c17 mRNA was also most abundant in the adrenal, followed by testis and ovary, but was undetectable in the placenta. P450c21 mRNA was detected only in the adrenal. None of these mRNAs was detected in kidney, liver, spleen, intestine, or muscle. Twenty-two fetal testis samples (13-25.8 weeks gestation) were studied. P450scc and P450c17 mRNAs were most abundant at 14-16 weeks and diminished to 35 and 19% of their peak values, respectively, by 20-25.8 weeks. Ovarian P450scc and P450c17 mRNAs were present, respectively, in only 6.2% and 1.8% of the maximum amount in the testis and did not vary detectably from 14.9 to 21.5 weeks gestation. The testicular and ovarian steroidogenic enzyme mRNA data correlate well with previously reported changes in gonadal steroidogenesis with gestational age. The presence of P450scc mRNA, but not P450c17 mRNA, in the placenta indicates that the placenta is able to initiate the synthesis of some steroid hormones, but is not able to synthesize estrogen de novo. Since P450c21 was found only in the adrenal, the extraadrenal 21-hydroxylation of progesterone to deoxycorticosterone, a common event in the fetus, is probably mediated by an enzyme(s) other than P450c21.

Tissue-specific expression and developmental regulation of the rat apolipoprotein B gene.

Abstract: Expression of the apolipoprotein B (apoB) gene was examined in a variety of fetal, neonatal, and adult rat tissues by probing RNA blots with a cloned rat apoB cDNA. Among 10 adult male tissues surveyed, small intestine had the highest concentration of apoB mRNA. Its abundance in liver and adrenal gland was 40% and 0.5%, respectively, of that in small bowel, while none was detected in colon, kidney, testes, spleen, lung, heart, or brain. ApoB mRNA is as abundant in 18-day fetal liver as at any subsequent period of hepatic development. In contrast, the concentration of apoB mRNA remains low in fetal intestine until the last (21st) day of gestation, when it increases sharply to levels that are several-fold higher than in the liver. ApoB mRNA levels in fetal membranes harvested during this late gestational period were 10 times greater than in fetal liver. Since the major lipoprotein species in 19-day fetal plasma is low density lipoprotein, these observations suggest that fetal liver, and particularly its functional homologue, the yolk sac, are the principal sites of fetal lipoprotein synthesis at this stage of development. A 20-fold increase in placental apoB mRNA concentrations during the last 48 hr of pregnancy (to a level that is 50% of that encountered in fetal membrane RNA) suggests a specific role for this organ in maternal-fetal lipid transport immediately prior to parturition. Pulse-labeling experiments using 21-day fetal tissue slices showed that the liver synthesizes both apoB-100 (B-PI) and apoB-48 (B-PIII) albeit in somewhat different ratios than the adult organ. Fetal intestine produces almost exclusively the smaller apoB species, while fetal membranes and placenta synthesize only the larger peptide. The postnatal pattern of apoB mRNA accumulation is similar in liver and intestine. Profound decreases were observed during the late suckling and weaning periods, followed by an increase to adult levels. These final concentrations were similar to those encountered at birth. Analysis of these developmental changes offers an opportunity to generate testable hypotheses about the factors that modulate apoB synthesis.

Temporal response of immunoreactive erythropoietin to acute hypoxemia in fetal sheep.

Abstract: . Acute hypoxemia was produced in chronically catheterized sheep fetuses to determine the response time necessary to increase plasma immunoreactive erythropoietin (Ep) concentration. Sodium nitrite (0.2 mM) was infused via a fetal vein to induce fetal hypoxemia. The resultant fetal methemoglobinemia was associated with a predictable, incremental decrease in arterial oxygen content. Twelve nitrite infusions were performed in eight fetal sheep preparations (gestational ages 115-146 days). Mean methemoglobin level increased to 33% of total Hb after 1- 2 h of NaNO2 infusion. These results were compared to those obtained in nine control studies in eight fetuses in which no change was observed for plasma Ep, arterial oxygen content, Pao2, pHa, or whole blood lactate. In the nitrite infused group, however, a significant and progressive increase in mean plasma Ep level over baseline levels was observed during the 4th and 5th h of hypoxemia (p<0.01). This change in Ep was significantly greater compared to the control group. These results, however, were confounded by the concomitant development of a lactic acidemia secondary to the fetal hypoxemia. To examine the theoretic possibility that lactic acidemia may primarily affect fetal Ep levels, an additional group of five fetuses was infused with L-lactic acid for the same time period. Although the decrements in pHa and whole blood lactate levels achieved in these fetuses were in excess of those observed during the nitrite infusions, this possibility was ruled out since no change in fetal plasma Ep levels occurred. We conclude that during the 4th h of acute fetal hypoxemia a predictable, progressive increase in plasma Ep level is observed. This response of plasma Ep to hypoxemia in late gestation fetal sheep is qualitatively similar to that observed in adult animals, thus demonstrating developmental maturity of the fetus.

Metabolic and circulatory studies of fetal lamb at midgestation.

Abstract: Uterine and umbilical blood flows, the placental clearance of 3H2O, uterine and umbilical uptakes of oxygen, glucose, and lactate were measured in conscious, pregnant sheep at 71-81 days gestation. Fetal weight was 210 +/- 20 g and less than half placental weight. In relation to fetal weight, umbilical flow was 468 +/- 57 ml X min-1 X kg-1, more than double normal values for the mature fetus. Clearance of 3H2O was approximately 12% of the late pregnancy value but high in relation to fetal weight (280 +/- 23 ml X min-1 X kg-1). Fetal oxygen uptake was 10.9 +/- 0.6 ml X min-1 X kg-1, approximately 40% greater than in late gestation. Umbilical uptake of glucose was also relatively high, whereas lactate uptake was low. Uteroplacental tissues consumed more than 80% of the oxygen and glucose taken up by the pregnant uterus. However, uteroplacental utilization rates of oxygen and glucose as well as net lactate production were lower (approximately 50, 30, and 25%, respectively) than in late pregnancy, despite a larger placental mass (486 +/- 22 vs. 302 +/- 12 g).

Regulation of pulmonary surfactant apoprotein SP 28-36 gene in fetal human lung.

Abstract: Pulmonary surfactant stabilizes lung alveoli, preventing respiratory failure and hyaline membrane disease in premature infants. In addition to lipids, surfactant contains apoproteins that are thought to be critical for normal surfactant function. We have examined the ontogeny and regulation of the major surfactant-associated protein of molecular mass 28-36 kDa (SP 28-36) in human fetal lung. SP 28-36 was not detected in tissue from second trimester abortuses by either immunoblot analysis or enzyme-linked immunosorbent assay (less than 0.02 microgram per mg of DNA). Levels of mRNA for SP 28-36, assayed by cDNA hybridization, were low or undetectable in all preculture specimens. The concentration of saturated phosphatidylcholine in lung tissue was 30% of the adult value with no apparent increase between 15 and 24 weeks gestation. SP 28-36 content increased during explant culture in the absence of serum and hormones, exceeding adult levels (3.2 +/- 1.0 micrograms per mg of DNA) after 5 days. In cultures treated with triiodothyronine (2 nM) and dexamethasone (10 nM), hormones that regulate phosphatidylcholine synthesis, the increase in SP 28-36 was accelerated (treated/control ratio was 7.1 and 3.4 at 3 and 5 days, respectively). Levels of mRNA for SP 28-36 also increased during culture and were stimulated by hormones (treated/control = 8.6 and 1.9 at 3 and 5 days, respectively). SP 28-36 and its mRNA increased similarly in the presence of dexamethasone alone, whereas triiodothyronine alone had no apparent effect. The molecular weight and charge pattern was similar for SP 28-36 of adult and cultured fetal tissue. These findings indicate that expression of the SP 28-36 gene is low during the second trimester, increases during explant culture, and is accelerated by glucocorticoid treatment.

Fetal growth and moderate drinking in early pregnancy

Abstract: Heavy maternal drinking during pregnancy has consistently been linked to decreased intrauterine growth, but the effect of smaller amounts of alcohol is less clear. In this study, the relationship between fetal growth and "moderate" drinking by low-risk, nonsmoking prenatal patients is explored. The sample consists of 144 women seen for the first time at the prenatal clinic of University College Obstetrics Hospital, London, England, between July 1979 and May 1980 and meeting the following criteria: white, aged 19-35 years, 8-16 weeks gestation at first prenatal visit, nonsmoker, nonalcoholic, lower middle class or higher, and in general good health. Average daily consumption of 10 g of ethanol (about one drink) in the week prior to recognition of pregnancy is related to a decrease in infant birth weight of 225 g, after adjustment for gestational age, sex of child, and maternal age, weight, height, pregnancy weight gain, social class, gravidity, and parity. In addition, consumption of this amount in the week before first prenatal visit is related to a comparable decrease in birth weight for male but not for female infants. These findings suggest that risk of decreased intrauterine growth begins very early in pregnancy, and that fetal response to later alcohol use may vary with sex of the child.

Abortion and Perinatal Sepsis Associated with Campylobacter Infection

Abstract: Fetal loss or neonatal sepsis associated with campylobacter infection during pregnancy is infrequently recognized. As reported herein, one case of premature labor and neonatal sepsis due to Campylobacter fetus subspecies fetus was treated successfully with ampicillin and gentamicin. Only 19 similar cases have been cited in the literature. A review of these 19 cases reveals that the Campylobacter species involved were probably C. fetus subspecies fetus in nine instances, Campylobacter jejuni in nine, and Campylobacter coli in one. There were no significant species-related differences in clinical presentation or outcome. Eighteen of 20 pregnancies (including tht described herein) ended prematurely at 13-32 weeks of gestation. All of the mothers survived, but fetal/neonatal mortality was 80%. The pathogenesis of campylobacter infection in this situation probably involves maternal bacteremia originating from the bowel, with subsequent feto-placental involvement. Early recognition and treatment may improve fetal/neonatal outcome.

Fetal allograft survival in immunocompetent recipients is age dependent and organ specific.

Abstract: This study explores whether fetal allograft survival is age dependent and organ specific. Fetal rat tissue (renal, gonadal, hepatic) from the third trimester of gestation (days 15-21) was transplanted into 306 outbred adult rats for 10-30 days. Grafts were studied by morphometric and histologic analysis. Ten days after implantation, renal tissue (N = 75) from late gestation (days 19-21) showed no increase in size. In contrast, 17-day fetal grafts (N = 20) grew 6.8 +/- 3.4 times,* while 15-day fetal grafts (N = 28) grew 17.5 +/- 6.1* times. (The symbol "*" indicates p less than 0.05, compared to original size). Twenty days after implantation, these 15-day fetal grafts (N = 20) grew 48.8 +/- 17.7* times. Ten days after grafting, the younger fetal tissue showed excellent maturation of renal elements and no sign of rejection; older fetal grafts had poor renal architecture and a dense lymphocytic infiltrate. The 15-day fetal gonadal tissue (N = 18) showed a moderate 10.6 +/- 3.2* increase in size while the 15-day hepatic grafts (N = 16) were regularly rejected within 10 days. Selected fetal allografts from early in the third trimester can not only survive but can grow and mature in an immunocompetent recipient. This fetal graft growth appears to be both age dependent and organ specific. The use of fetal organs may broaden the potential pool for transplantation. However, further studies are needed to define the ontogeny of graft acceptance.

Human fetal adenohypophysis. Histologic and immunocytochemical analysis.

Abstract: One hundred and forty human fetal pituitary glands were removed from fetuses at 7-40 weeks of gestation and studied by light microscopy and immunocytochemistry to localize adenohypophysial hormones. For immunocytology, the avidin-biotin-peroxidase complex technique was more sensitive and identified hormones in younger fetuses than did the immunoperoxidase method. Adrenocorticotrophin, beta-endorphin, and growth hormone were the first hormones detected; they were identified by intense cytoplasmic immunopositivity at 8 weeks of gestation. Between 10 and 20 weeks, many growth hormone containing cells were large and showed scattered, faint positivity; after 20 weeks, smaller cells with intense positivity predominated. alpha-Subunit of the glycoprotein hormones was identified at 9 weeks of development; beta-subunits of thyroid-stimulating hormone, follicle-stimulating hormone, and luteinizing hormone appeared by 12 weeks. Gonadotrophs differed in numbers related to fetal age and sex. From 15 to 25 weeks, glands of female fetuses contained more gonadotrophs than did those of males; after 25 weeks, there was no significant difference in total gonadotroph numbers. Throughout gestation, adenohypophyses of male fetuses had more luteinizing hormone containing cells than follicle-stimulating hormone containing cells; pituitaries of females had approximately the same numbers of follicle-stimulating hormone containing and luteinizing hormone containing cells. Prolactin was identified in few small cells at 12 weeks; at term, prolactin-containing cells were numerous, comparable to those seen in the hyperplasia of maternal glands in late gestation and during lactation. This comprehensive study indicates morphologic correlations with pituitary hormone extraction data and with the appearance of the various hormones in the fetal circulation.

Effects of maternal iodine deficiency on the L-thyroxine and 3,5,3'-triiodo-L-thyronine contents of rat embryonic tissues before and after onset of fetal thyroid function.

Abstract: Female rats were placed on a low iodine diet (LID) or LID supplemented with KI. They were mated 3-6 months later. Maternal and embryonic tissues were otained both before the onset of fetal thyroid function, at 11 and 17 days of pregnancy, and at 21 days of gestation. T4 and T3 concentrations were measured by RIA. T4 concentrations were very low in the plasma, liver, and lung of LID dams and in all embryonic samples obtained from such mothers, namely 11-day-old embryotrophoblasts, 17-day-old placentas and embryos, 21-day-old placentas, embryos, plasma, liver, lung, and carcass (whole embryos minus the trachea, thyroid, blood, liver, and brain). T3 was low in 17- day-old placentas and embryos and in all fetal tissues obtained at 21 days of gestation from LID dams. These results show that when iodine deficiency is severe enough to result in very low maternal plasma T4 levels, embryonic tissues are deficient in T4 and T3 both before and after the onset of fetal thyroid function. This finding might be relevant...

Metabolism of the gravid uterus, foetus and utero-placenta at several stages of gestation in cows

Abstract: To quantify changes in rates of metabolism and nutrient uptake of gravid uteiine, foetal and utero-placental tissues throughout gestation, mature Hereford cows received surgery at 132 ± 0·6 (n = 12), 176 ± 0·5 (n = 8), 220 ±0·4 (n = 11) and 245 ±1·5 (n = 7) days after mating. Indwelling catheters were implanted into a uterine artery and vein of all cows. Foetal catheters also were implanted into an umbilical vein and foetal femoral artery and vein (days 176 and 220) or into a placental artery and two placental veins (days 132 and 245). Approximately 5 days after surgery, deuterium oxide was infused into a foetal femoral venous or placental venous catheter during a 3 h period to quantify uterine and umbilical blood flows by steady-state diffusion methods. Oxygen, glucose, lactate and α-amino acid nitrogen concentrations were determined for uterine and foetal blood samples collected during this procedure.Uterine blood flow increased 4·5-fold (2·92–13·181/min) and umbilical blood flow increased 21-fold (0·28–5·861–min) during the interval of gestation studied. The relative rate of increase of umbilical blood flow was about twice as great as that of uterine blood flow. Uterine arterial and umbilical venous concentrations as well as uterine arterial-venous and umbilical venous-arterial concentration differences in metabolites changed little with stage of gestation. However, because rates of blood flow increased, uptakes of O2, glucose and α-amino N by the gravid uterus and foetus increased as gestation advanced. The proportion of gravid uterine uptakes utilized by the foetus increased from day 137 to 226 for O2 (24–58%) and from day 137 to 180 for glucose (4–19%), then remained relatively constant. The proportion of gravid uterine α-amino N uptake utilized by the foetus remained relatively constant and averaged 60%. A net secretion of lactate from the utero-placenta to the uterine and foetal circulations was observed and increased as gestation advanced. These data indicate that increased rates of uptake or secretion of metabolites by tissues of the gravid uterus can be explained primarily by increased rates of uterine and umbilical blood flows.

Prediction and therapy of intrauterine and late-onset neonatal hyperthyroidism.

Abstract: These studies in a mother and child describe the effects of multiple antibodies directed against the TSH receptor that influenced thyroid function in the fetus and infant. Blood was taken periodically for 6 months from a child (C3) whose mother (M) was known to have in her serum immunoglobulin G (IgG) that contained thyroid-stimulating antibody (TSAb), an inhibitor of TSAb and TSH binding and action, and an enhancer of TSH binding to its receptor, the last activity presumed to enhance both TSH and TSAb action. We correctly predicted that C3 and an older sibling, C2, would have delayed onset of hyperthyroidism (∼45 days of age) due to interaction of these antibodies. In addition, in both C2 and C3, fetal hyperthyroidism in the second trimester was postulated, and therefore, M was given propylthiouracil from then until term (C2) or 8 months (C3), with associated return of the fetal heart rate to normal in the one fetus (C3) in whom this was monitored. IgG was purified from C3's serum samples and tested for ...