Showing papers on "Fetus published in 1992"

Fetal nuchal translucency: ultrasound screening for chromosomal defects in first trimester of pregnancy.

Abstract: OBJECTIVE--To examine the significance of fetal nuchal translucency at 10-14 weeks' gestation in the prediction of abnormal fetal karyotype. DESIGN--Prospective screening study. SETTING--The Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London. SUBJECTS--827 fetuses undergoing first trimester karyotyping by amniocentesis or chorionic villus sampling. MAIN OUTCOME MEASURE--Incidence of chromosomal defects. RESULTS--The incidence of chromosomal defects was 3% (28 of 827 cases). In the 51 (6%) fetuses with nuchal translucency 3-8 mm thick the incidence of chromosomal defects was 35% (18 cases). In contrast, only 10 of the remaining 776 (1%) fetuses were chromosomally abnormal. CONCLUSION--Fetal nuchal translucency > or = 3 mm is a useful first trimester marker for fetal chromosomal abnormalities.

Fetal and Neonatal Physiology

Abstract: Section I - Genetics and Embryology Basic Genetic Principles Prenatal Diagnosis Basic Embryology Regulation of Embryogenesis The Extracellular Matrix in Development Stem Cell Biology Apoptotic Cell Death Angiogenesis Epigenetics Section II - Placenta and Intrauterine Environment Placental Development Regulation of the Placental Circulation Mechanisms of Transfer Across the Human Placenta Endocrine and Paracrine Function of the Human Placenta Fetal and Maternal Responses to Intrauterine Infection Fetal Origins of Adult Disease: A Classic Hypothesis with New Relevance Physiologic Effects of Multiple Pregnancy on Mother and Fetus Placental function in intrauterine growth restriction Section III - Developmental Pharmacology and Pharmacokinetics Basic Pharmacologic Principles Principles of Pharmacokinetics Physicochemical and Structural Properties Regulating Placental Drug Transfer Pharmacogenetics Drug Distribution in Fetal Life Drug Transfer During Breastfeeding Section IV - Intrauterine and Postnatal Growth Circulatory and Metabolic Changes Accompanying Fetal Growth Restriction Endocrine Factors Affecting Neonatal Growth Human Milk Composition and Function in the Infant Physiology of Lactation Section V - Perinatal Iron, Mineral, and Vitamin Metabolism Fetal and Neonatal Iron Metabolism Neonatal Calcium, Phosphorus, and Magnesium Homeostasis Zinc in the Fetus and Neonate Vitamin A Metabolism in the Fetus and Neonate Vitamin E Metabolism in the Fetus and Newborn Infant Vitamin K Metabolism in the Fetus and Neonate Section VI - Lipid Metabolism Maternal-Fetal Transfer of Lipid Metabolites Brown Adipose Tissue: Development and Function Lipids as an Energy Source for the Premature and Full-Term Neonate Ketone Body Production and Metabolism in the Fetus and Neonate Long-Chain Fatty Acids in the Developing Retina and Brain Section VII - Carbohydrate Metabolism Metabolism of Glucose and Methods of Investigation in the Fetus and Newborn Carbohydrate Metabolism During Pregnancy Oxygen Consumption and General Carbohydrate Metabolism of the Fetus Role of Glucoregulatory Hormones in Hepatic Glucose Metabolism During the Perinatal Period Cell Glucose Transport and Glucose Handling During Fetal and Neonatal Development Section VIII - Protein Metabolism General Concepts of Protein Metabolism Fetal Requirements and Placental Transfer of Nitrogenous Compounds Section IX - Thermoregulation Temperature Control in Newborn Infants Responses of the Fetus and Neonate to Hypothermia Section X - Skin Structure and Development of Skin and Cutaneous Appendages Physiologic Development of the Skin Section XI - Fetal and Neonatal Cardiovascular Physiology Cardiovascular Development Developmental Electrophysiology in the Fetus and Neonate Developmental Biology of the Pulmonary Vasculature Development of the Gastrointestinal Circulation in the Fetus and Newborn Physiology of Congenital Heart Disease in the Neonate Neural Regulation of Blood Pressure During Fetal and Newborn Life Developmental Effects on Fetal Circulation Mechanisms Regulating Closure of the Ductus Arteriosus Umbilical Circulation Fetal and Placental Circulation During Labor Physiology of Resuscitation Section XII - The Lung Normal and Abnormal Structural Development of the Lung Regulation of Alveolarization Physiologic Mechanisms of Normal and Altered Lung Growth Before and After Birth Molecular Mechanisms of Lung Development and Lung Branching Morphogenesis Regulation of Liquid Secretion and Absorption by the Fetal and Neonatal Lung Upper Airway Structure: Function, Regulation, and Development Regulation of Lower Airway Function Functional Development of Respiratory Muscles Mechanics of Breathing Pulmonary Gas Exchange in the Developing Lung Oxygen Transport and Delivery Control of Breathing in Fetal Life and Onset and Control of Breathing in the Neonate Basic Mechanisms of Oxygen Sensing and Response to Hypoxia Evaluation of Pulmonary Function in the Neonate Mechanisms of Neonatal Lung Injury Impaired Lung Growth After Injury in Premature Lung Antenatal Factors That Influence Postnatal Lung Development and Injury Regulation of Pulmonary Circulation Section XIII - Surfactant Historical Perspective Composition of Pulmonary Surfactant Lipids and Proteins Structure And Development of Alveolar Epithelial Cells Regulation of Surfactant-Associated Phospholipid Synthesis and Secretion Hormonal Therapy for Prevention of Respiratory Distress Syndrome Surfactant Treatment Genetics and Physiology of Surfactant Protein Deficiencies Section XIV - Physiology of Gastrointestinal Tract in the Fetus and Neonate Trophic Factors and Regulation of Gastrointestinal Tract and Liver Development Organogenesis of the Gastrointestinal Tract Development of the Enteric Nervous System Development of Gastric Secretory Function Development of Gastrointestinal Motility Development of the Exocrine Pancreas Digestive-Absorption Functions in Fetuses, Infants, and Children Development of the Intestinal Microbiome Section XV - Liver and Bilirubin Metabolism Organogenesis and Histologic Development of the Liver Bile Acid Metabolism During Development Neonatal Bilirubin Metabolism Hereditary Contribution to Neonatal Hyperbilirubinemia Mechanisms of Action of Phototherapy for Neonatal Hyperbilirubinemia Section XVI - The Kidney Embryogenesis and Anatomic Development of the Kidney Functional Development of the Kidney in Utero Development and Regulation of Renal Blood flow in the Neonate Development of the Renin-Angiotensin System Postnatal Development of Glomerular Filtration Rate in Neonates Renal Transport of Sodium During Early Development Potassium Homeostasis in the Fetus and Neonate Role of the Kidney in Calcium and Phosphorus Homeostasis Transport of Amino Acids in the Fetus and Neonate Developmental Aspects of Organic Acid Transport Concentration and Dilution of the Urine Development of Acidification Mechanisms in the Fetus and Neonate Response to Nephron Loss in Early Development Section XVII - Fluid and Electrolyte Metabolism Fluid Distribution in the Fetus and Neonate Regulation of Acid-Base Balance in the Fetus and Neonate Section XVIII - Developmental Hematopoiesis Developmental Biology of Stem Cells: From the Embryo to the Adult Developmental Granulocytopoiesis Developmental Erythropoiesis Developmental Megakaryocytopoiesis Section XIX - Hemostasis Developmental Hemostasis Platelet-Vessel Wall Interactions Section XX - Developmental Immunobiology Host Defense Mechanisms Against Bacteria Host-Fungi Interactions Relevant to the Newborn Infant Host Defense Mechanisms Against Viruses T-Cell Development B-Cell Development Mononuclear Phagocyte System Normal and Abnormal Neutrophil Physiology in the Newborn The Complement System of the Fetus and Newborn Cytokines and Inflammatory Response in the Fetus and Neonate Immunology of Human Milk and Host Immunity Neonatal Pulmonary Host Defense Section XXI - Neurology Development of the Nervous System Development of the Blood-Brain Barrier Trophic Factor and Nutritional and Hormonal Regulation of Brain Development Intraventricular Hemorrhage in the Neonate Cerebellar Development - an Impact of Preterm Birth and Co-Morbidities Electroencephalography in the Premature and Full-Term Infant Developmental Aspects of Pain Section XXII - Special Sensory Systems in the Fetus and Neonate Early Development of the Human Auditory System Development of Taste and Smell in the Neonate Section XXIII - Orthopedics The Growth Plate: Embryologic Origin, Structure, and Function Ontogenesis of Striated Muscle Section XXIV - Endocrine Function Hypothalamus: Neuroendometabolic Center Growth Factor Regulation of Fetal Growth Growth Hormone in the Fetus and Newborn Luteinizing Hormone and Follicle-Stimulating Hormone Secretion in the Fetus and Newborn Development of the Corticotropin-Releasing Hormone-Corticotropin System in the Mammalian Fetus Fetal and Neonatal Adrenocortical Physiology Fetal and Neonatal Thyroid Physiology Section XXV - Ovary and Testis Genetics of Sex Determination and Differentiation Differentiation of the Ovary Testicular Development and Descent Section XXVI - Pathophysiology of Neonatal Diseases Pathophysiology of Neonatal sepsis Pathophysiology of Hypoglycemia in the Neonate Pathophysiology of Cardiomyopathies Pathophysiology of Persistent pulmonary hypertension of the newborn Pathophysiology of Shock in the Fetus and Neonate Pathophysiology of Apnea of Prematurity Pathophysiology of Respiratory Distress Syndrome Pathophysiology of Meconium Aspiration Syndrome Pathophysiology of Bronchopulmonary Dysplasia Pathophysiology of Ventilator Dependent Infants Pathophysiology of Gastroesophageal Reflux Pathophysiology of Neonatal Necrotizing Enterocolitis Pathophysiology of Kernicterus Pathophysiology of neonatal acute kidney injury Pathophysiology of Edema Pathophysiology of Retinopathy of Prematurity Pathophysiology of Hypoxic-ischemic Brain Injury Pathophysiology of Neonatal White Matter Injury Pathophysiology of Meningitis Pathophysiology of Neural Tube Defects Pathophysiology of Preeclampsia Pathophysiology of Preterm Birth Pathophysiology of Chorioamnionitis

Birth weight and perinatal mortality: the effect of gestational age.

Abstract: BACKGROUND. The strong association between birth weight and perinatal mortality is due both to gestational age and to factors unrelated to gestational age. Conventional analysis obscures these separate contributions to perinatal mortality, and overemphasizes the role of birth weight. An alternative approach is used here to separate gestational age from other factors. METHODS. Data are from 400,000 singleton births in the Norwegian Medical Birth Registry. The method of Wilcox and Russell is used to distinguish the contributions to perinatal mortality made by gestational age and by relative birth weight at each gestational age. RESULTS. Gestational age is a powerful predictor of birth weight and perinatal survival. After these effects of gestational age are controlled for, relative birth weight retains a strong association with survival. CONCLUSIONS. Current public health policies in the United States emphasize the prevention of low birth weight. The present analysis suggests that the prevention of early de...

Developmental regulation of GLUT-1 (erythroid/Hep G2) and GLUT-4 (muscle/fat) glucose transporter expression in rat heart, skeletal muscle, and brown adipose tissue.

Abstract: The expression of GLUT-1 (erythroid/Hep G2) and GLUT-4 (muscle/fat) glucose transporters was assessed during development in rat heart, skeletal muscle, and brown adipose tissue. GLUT-4 protein expression was detectable in fetal heart by day 21 of pregnancy; it increased progressively after birth, attaining levels close to those of adults at day 15 post natal. In contrast, GLUT-4 messenger RNA (mRNA) was already present in hearts from 17 day-old fetuses. GLUT-4 mRNA stayed low during early postnatal life in heart and brown adipose tissue and only increased after day 10 post natal. The expression pattern for GLUT-4 protein in skeletal muscle during development was comparable to that observed in heart. In contrast to heart and skeletal muscle, GLUT-4 protein in brown adipose tissue was detected in high levels (30% of adult) during late fetal life. During fetal life, GLUT-1 presented a very high expression level in brown adipose tissue, heart, and skeletal muscle. Soon after birth, GLUT-1 protein diminished progressively, attaining adult levels at day 10 in heart and skeletal muscle. GLUT-1 mRNA levels in heart followed a similar pattern to the GLUT-1 protein, being very high during fetal life and decreasing early in post natal life. GLUT-1 protein showed a complex pattern in brown adipose tissue: fetal levels were high, decreased after birth, and increased subsequently in post natal life, reaching a peak by day 9. Progesterone-induced postmaturity protected against the decrease in GLUT-1 protein associated with post natal life in skeletal muscle and brown adipose tissue. However, GLUT-4 induction was not blocked by postmaturity in any of the tissues subjected to study. These results indicate that: 1) during fetal and early post natal life, GLUT-1 is a predominant glucose transporter isotype expressed in heart, skeletal muscle, and brown adipose tissue; 2) during early post natal life there is a generalized GLUT-1 repression; 3) during development, there is a close correlation between protein and mRNA levels for GLUT-1, and therefore regulation at a pretranslational level plays a major regulatory role; 4) the onset of GLUT-4 protein induction occurs between days 20-21 of fetal life; based on data obtained in rat heart and brown adipose tissue, there is a dissociation during development between mRNA and protein levels for GLUT-4, suggesting modifications at translational or posttranslational steps; and 5) postmaturity blocks the decrease in GLUT-1 expression but not the induction of GLUT-4, observed soon after birth.(ABSTRACT TRUNCATED AT 400 WORDS)

Cerebral Histologic and Electrocorticographic Changes after Asphyxia in Fetal Sheep

Abstract: Asphyxia can cause neurologic damage in the fetus, hot there are few data relating severity or duration of asphyxia to the degree of cerebral damage. We report cerebral histologic and electrophysiologic changes after asphyxia in chronically instrumented late-gestation fetal sheep. We reduced uterine blood flow to produce an ascending aortic blood oxygen content 7.0 in five of six without damage (p < 0.05). We conclude that severe intrauterine asphyxia for periods of 30 to 120 min can cause predominant parasagittal neuronal death and that this is associated with hypotension, severe metabolic acidosis, and suppression of EEC during the insolt. These data are consistent with the suggestion that impairment of cerebral perfusion is a critical event in localizing cerebral damage during perinatal asphyxia.

Fetal cells in the maternal circulation.

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

Gene expression of insulin-like growth factors (IGFs), the type 1 IGF receptor, and IGF-binding proteins in dexamethasone-induced fetal growth retardation.

Abstract: Altered gene expression and/or actions of the insulin-like growth factors (IGFs) have been implicated in the mediation of both pre- and postnatal growth retardation secondary to glucocorticoid excess. To investigate this possibility, we assessed the gene expression of the IGFs, the type I IGF receptor, and IGF-binding proteins (IGFBPs) in 20-day gestation liver and lung of growth-retarded fetuses whose mothers were treated with dexamethasone (DXM; 100 micrograms, ip, daily) on gestation days 15-19 (gestation = 21-22 days). DXM treatment in dams produced fetal growth retardation without decreasing litter size (32% decrease in fetal body weight). Both fetal liver and lung demonstrated decreased wet weight (48% and 47%, respectively) and DNA content (65% and 51%, respectively) compared to control animals. Our results suggest that increased expression of IGFBP-1, and possibly IGFBP-2, is involved in mediating the marked growth retardation. As assessed by solution hybridization assays and Northern blot analysi...

Detection of fetal cells with 47,XY,+21 karyotype in maternal peripheral blood.

Abstract: Fetal cells were isolated from the peripheral blood of a pregnant woman at 19 weeks of gestation whose fetus had Down syndrome. An amniocentesis had been performed 2 weeks earlier because of abnormalities detected on an antenatal sonogram. Fetal cells were separated by fluorescence-activated cell sorting using monoclonal antibody to the transferrin receptor (TfR). Fluorescence in situ hybridization studies with probes for chromosomes Y and 21 revealed a small number of 47,XY,+21 cells in the TfR+ sorted fraction. Although preliminary, the results of this study suggest the possibility that one day, fetal chromosome aneuploidy will be routinely diagnosed from maternal venous blood samples.

Prenatal expression of the growth hormone (GH) receptor/binding protein in the rat: a role for GH in embryonic and fetal development?

Abstract: Although fetal growth is generally considered to be independent of pituitary growth hormone (GH), it is possible that pituitary GH plays a modulatory role in organ development or that a GH-like substance of non pituitary origin may influence fetal growth through the GH receptor. Accordingly, we have used immunohistochemistry, northern blot analysis, the reverse transcriptase-polymerase chain reaction and solution hybridization to study the ontogeny of the GH receptor/binding protein (BP) from the 12-day-old embryo (E12) to the E18 rat fetus. GH receptor/BP immunoreactivity was observed in all major organ systems of the E18 rat fetus and was not preferentially associated with any germ layer derivative. A general increase in GH receptor/BP immunoreactivity was evident from E12 to E18, with a marked increase occurring between E16 and E18. Hemangioblastic tissue was, however, strongly or intensely immunoreactive at all stages of development, as was the placenta. Most noteworthy of the other tissues expressing GH receptor/BP immunoreactivity by day 18 were skeletal and smooth muscle, chondroprogenitor cells, epithelial lining cells, neuronal ganglia, ependymal cells and the adrenal cortex. In the placenta, the most prominent immunoreactivity was associated with decidual cells. Total RNA was isolated from E12 to E18 rat fetuses and adult rat liver. Northern hybridization with a 35S-labelled rat GH receptor cRNA probe revealed that 3.9 kb and 1.2 kb transcripts complementary to the rat GH receptor riboprobe are present from at least E16. The existence of GH receptor mRNA at E12 and E14 was demonstrated by the polymerase chain reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Multidrug resistance gene (P-glycoprotein) expression in the human fetus.

Abstract: P-glycoprotein, a transmembrane protein associated with multidrug resistance in cancer cells, is also expressed in normal tissues. To get more insight into the physiologic role of mdr1/P-glycoprotein, we investigated its expression in human fetal tissues after 7 to 38 weeks of gestation by an immunohistochemical technique, using three different monoclonal antibodies, and by a sensitive RNAse protection assay. Expression of mdr1-mRNA could already be demonstrated in the embryonal phase of human development, after 7 weeks of gestation. Comparing the adult with the fetal tissue distribution, differences were found in specific organs, such as adrenal, intestine, respiratory epithelium, and brain capillaries. In the fetal zone cells of the fetal adrenal cortex no staining was observed by immunohistochemistry, whereas the definitive zone showed increasing expression throughout gestation. Prenatal intestine did not show staining of the epithelium, although definite mdr1-mRNA expression was observed in late specimens. Interestingly, respiratory epithelium of main bronchi and pharynx, not expressing P-gp in adults, did stain positive. Expression of P-gp in brain capillaries was not observed before the third trimester of pregnancy, whereas in kidney and liver, mdr1-mRNA expression and staining for P-glycoprotein were detected in early fetal life (11 to 14 weeks). These findings suggest a pivotal role of P-glycoprotein in physiology of various organs already in early phases of human development and may help to identify its physiologic substrates.

Fetal thyroid function.

Abstract: Cordocentesis has permitted the study of fetal thyroid function in utero. In normal fetuses, fetal TSH, TBG, and thyroid hormone concentrations increase progressively throughout intrauterine life. Fetal TSH concentrations are always high compared to nonpregnant adult values. TBG concentrations reach adult levels at term. TT4 and FT4 concentrations reach adult levels at approximately 36 weeks gestation, but TT3 and FT3 are always below adult concentrations. There are no significant associations between fetal and maternal concentrations of TSH, TBG, or thyroid hormones. The maternal administration of TRH from at least 25 weeks gestation stimulates the fetal pituitary gland to produce TSH. The response is rapid, unrelated to gestational age, and much greater than that of the mother. These findings suggest that in intrauterine life there is independent and autonomous maturation of the pituitary, thyroid, and liver. The fetal pituitary is able to respond to the maternal administration of TRH and appears to be more sensitive than in the adult. In small-for-gestational-age fetuses, the concentrations of TSH are higher and the concentrations of TT4 and FT4 are lower than in appropriately grown fetuses. The degrees of elevation of TSH and fall in thyroid hormones are significantly related to the degree of fetal hypoxemia and acidemia, respectively. Although the low concentrations of thyroid hormones may have some beneficial effects by reducing oxygen requirements, they may adversely affect brain development.

Transport of steroids between fetuses via amniotic fluid in relation to the intrauterine position phenomenon in rats.

Abstract: In litter-bearing mammals, the course of development of male and female fetuses is affected by the presence of other fetuses of the same or opposite sex located nearby within the uterus. The transport of testosterone between rat fetuses was examined by implanting a Silastic capsule containing [3H]testosterone into the amniotic sac of a fetus at either the ovarian or cervical end of a uterine horn on days 19 and 20 of pregnancy. The amount of testosterone that was recovered from the amniotic fluid of other fetuses 12 h later was determined. The amniotic fluid surrounding the adjacent fetus on the cervical side of the implanted fetus contained three times as much [3H]testosterone as did the adjacent fetus on the ovarian side, regardless of where in the uterus the implant was made. The movement of dye injected into the uterine lumen was towards the cervix. Intraluminal fluid movement may thus mediate the greater transport of [3H]testosterone towards the cervix than towards the ovary. Our findings support the hypothesis that transport of testosterone between fetuses occurs across the fetal membranes via diffusion, such that any fetus (male or female) located between male fetuses receives the greatest supplement of testosterone.

Development of intestinal mucosal immunity in fetal life and the first postnatal months.

Abstract: Nine premature infants who were either stillborn or who died shortly after delivery (gestational age, 24-32 wk), eight full-term infants who died during the first 3 postnatal wk, and four infants who died in the postneonatal period were studied by immunohistochemistry for duodenal expression of secretory component (SC) and epithelial HLA class I and II determinants and for the presence of IgA-, IgM-, and IgG-producing immunocytes. Only small amounts of SC appeared before the 29th gestational wk, but thereafter it increased rapidly; 1 wk after birth, SC showed an adult distribution pattern. Epithelial class I was expressed throughout the period investigated, whereas class II (HLA-DR) determinants were absent on the duodenal villi until 1 wk after birth. HLA-DP and -DQ were not expressed by the epithelium. No IgA immunocytes were seen before 1 wk after birth, whereas a few IgM- and IgG-producing cells were present throughout the period studied. The intense epithelial HLA-DR expression from the 2nd postnatal wk, along with SC and the appearance of IgA immunocytes, suggests that the intestinal immune system is modulated in response to environmental factors shortly after birth.

Immunodetection of Estrogen Receptors in Fetal and Neonatal Female Mouse Reproductive Tracts

Abstract: Immunodetection methods were used to detect estrogen receptors (ER) in male reproductive tracts on fetal days 13, 15, and 17 and on the day of birth. Immunocytochemistry revealed that most of the cells of the gonad and associated Wolffian duct stained for ER on fetal day 13. During the next 6 days, ER distribution changed, and by the day of birth, ERs were observed only in epithelial cells of the epididymis (derived from the Wolffian duct) and in a portion of cells from the testis. Immunoblots confirmed that a band the size of the ER stained in reproductive tracts for all ages studied. Similar to the fetal female, ERs are present throughout the early development of the fetal male reproductive tract. However, in contrast to the female, ERs appear to decrease in the male fetal reproductive tract at the time of birth.

Neospora-like protozoal infections associated with abortion in goats.

Abstract: Neospora caninum was first identified and described in 1988 from a litter of puppies with encephalomyelitis. Since this first report, naturally occurring neonatal or fetal infections caused by Neospora-like protozoa have been described in cattle, sheep, and horses. Abortion or neonatal infection in cattle by this Neospora-like protozoa have been reported throughout the United States and in several other countries. Additionally, experimental infections have been produced in cats, rats, and mice. We report on 2 unrelated cases of abortion associated with a Neospora-like protozoan in pygmy goats. The first fetus and placenta (Fetus A), from a 2-year-old doe, were submitted in November 1989 from a small farm east of Sacramento, California. The doe had an uneventful pregnancy the previous year. The owner reported that abortions had occurred in 3 other does during the previous 2 years. These fetuses had been necropsied, but the etiology in each case was undetermined. No additional history on the flock was available. The fetus was 130 days gestational age and had a 24-cm crown-rump length. It was autolyzed, with blood staining of tissues and large amounts of deep red serous fluid in the body cavities. There were no significant gross pathologic findings. The placenta was very edematous. The second fetus and placenta (Fetus B) were submitted in March 1991 from a farm in the Sacramento Valley north of Sacramento, California. There was no history on this flock. The fetus had a 14-cm crown-rump length with no body hair. It was partially mummified with a small amount of fetal fluid in the thorax. There were no significant gross pathologic findings. Bacterial cultures of placenta, lung, liver, and abomasal fluid, darkfield examination of abomasal fluid, Chlamydial and viral cultures of pooled tissues, fluorescent antibody tests of kidney and placental impression smears for Leptospira spp. and Chlamydia psittaci, respectively, were performed as previously described and were all negative for both fetuses. Fluorescent antibody tests for border disease using frozen sections of liver and lung were negative in both fetuses. The total immunoglobulin G level in fluid from Fetus A was 2,720 mg/dl and in Fetus B was > 100 mg/dl. There was no antibody to Brucella ovis (enzyme-linked immunosorbent assay), bluetongue virus (agar-gel immunodiffusion), Leptospira spp. (microagglutination test), or Toxoplasma gondii (latex agglutination at a 1:16 dilution) in either fetus. Nitrate

Localization of the growth hormone receptor, identified by immunocytochemistry, in second trimester human fetal tissues and in placenta throughout gestation

Abstract: Pituitary GH secretion appears largely unnecessary for the attainment of normal birth size in many species, including man. This is believed to be due to an immaturity and/or an absence of GH receptors in many fetal tissues. However, in vitro studies using late first trimester human fetal tissues have demonstrated mitogenic actions of GH on liver and stimulation of insulin biosynthesis in pancreas. To resolve this discrepancy, we have employed immunocytochemistry to identify the presence and distribution of GH receptors in various human fetal tissues. Fetuses of 14-16 weeks gestation were obtained after therapeutic abortion, tissues were fixed, and immunocytochemistry was performed using monoclonal antibodies against purified rat or rabbit GH receptor. The specificity of staining was confirmed by preabsorption of the antibodies with 1) adult rat liver membranes or 2) human fetal liver membranes, both of which possess specific GH-binding sites, or 3) human fetal skeletal muscle membranes, which do not speci...

Disorders of the Placenta, Fetus, and Neonate: Diagnosis and Clinical Significance

Abstract: The ancient mechanisms that regulate human reproductive performance environmental influences on the embryo and early foetus maternal nutrition and pregnancy outcome foetal growth, effects of maternal cigarette smoking on the foetus and neonate disorders of the umbilical cord disorders of the placenta and decidua disorders of the foetal membranes preterm birth disorders of twins disorders of the central nervous system differing effects of male and female foetuses on pregnancy outcome being an expert witness - claims of birth injury.

Elevating maternal insulin-like growth factor-I in mice and rats alters the pattern of fetal growth by removing maternal constraint.

Abstract: Fetal growth is normally constrained by maternal factors. This constraint is demonstrated by the usual inverse linear relationship between litter size and mean fetal weight. Cross-breeding experiments between mice of lines selected for high or low plasma insulin-like growth factor (IGF-I) levels suggested that elevations in maternal IGF-I abolish (P less than 0.01) this constraining effect and reverse the usual positive relationship between fetal and placental size in late gestation. This was confirmed by treating mice and rats throughout pregnancy with IGF-I. In normal mice and in low IGF-I line mice treatment with IGF-I (10 micrograms 8-hourly s.c. from day 1 to 19 of pregnancy) abolished maternal constraint whereas 0.9% (w/v) NaCl treatment did not. In Wistar rats osmotic pumps were implanted to deliver IGF-I (1 microgram/g body weight per day), bovine GH (bGH; 0.6 microgram/g body weight per day) or saline from day 1 to 19 of pregnancy. IGF-I therapy but not bGH or saline abolished (P less than 0.01) maternal constraint and altered (P less than 0.01) the relationship between placental and fetal weight. When high or low IGF-I line mice embroys were transplanted into a normal line of mice, the expected negative relationship (P less than 0.05) between mean fetal weight and litter size was maintained. However, the embryos of the high line were heavier (P less than 0.05) than those from the low line irrespective of fetal number, suggesting a direct role for IGF-I in the regulation of fetal growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal iron and cytochrome c status after intrauterine hypoxemia and erythropoietin administration.

Abstract: Chronic fetal hypoxemia stimulates erythropoiesis and may result in a redistribution of fetal iron from plasma into erythrocytes. We studied the response of fetal plasma erythropoietin (Ep) to hypoxemia, the role of Ep in stimulating erythropoiesis in utero, and the effect of augmented erythropoiesis on fetal plasma Ep and iron and tissue cytochrome c concentrations in 19 chronically instrumented late-gestation fetal sheep. The fetuses were stimulated to produce 28 erythropoietic responses after exposure to 1) acute hypoxemia (1-5 days), 2) chronic hypoxemia (greater than 7 days), and/or 3) administration of 1,500 U recombinant human Ep concurrently during normoxemia. Plasma Ep peaked less than 12 h after the onset of hypoxemia or Ep bolus. Plasma iron decreased 24-48 h later and returned to baseline 48-96 h after normalization of Ep levels to baseline. The plasma iron response was directly related to the erythropoietin stimulus (r = 0.79, P less than 0.001) and inversely related to liver iron concentration at death (r = -0.84, P less than 0.001). Nine fetuses with depleted liver iron concentrations at autopsy had significantly lower heart and skeletal muscle iron concentrations compared with animals with 10% of control liver iron remaining. Skeletal muscle and heart iron and cytochrome c concentrations were significantly correlated. Ep has a potent biological effect on fetal erythropoiesis and iron metabolism. Augmented fetal erythropoiesis, mediated by Ep, results in decreased plasma iron, hepatic storage iron, and skeletal and cardiac muscle iron and cytochrome c. The model potentially explains the iron abnormalities found in newborn infants after fetal hypoxia.

Expression of the insulin-like growth factor-II/mannose-6-phosphate receptor in multiple human tissues during fetal life and early infancy.

Abstract: The insulin like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor has been detected in many cells and tissues. In the rat, there is a dramatic developmental regulation of IGF-II/M6P receptor expression, the receptor being high in fetal and neonatal tissues and declining thereafter. We have systematically studied the expression of the human IGF-II/M6P receptor protein in tissues from 10 human fetuses and infants (age 23 weeks gestation to 24 months postnatal). We have asked 1) whether there is differential expression among different organs, and 2) whether or not the human IGF-II/M6P receptor is developmentally regulated from 23 weeks gestation to 24 months postnatal. Protein was extracted from human tissues using a buffer containing 2% sodium dodecyl sulfate and 2% Triton X-100. Aliquots of the protein extracts were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting using an anti-IGF-II/M6P receptor antiserum (no. 66416) and 125I-protein A or an immunoperoxidase stain. IGF-II/M6P receptor immunoreactivity was detected in all tissues studied with the highest amount of receptor being expressed in heart, thymus, and kidney and the lowest receptor content being measured in brain and muscle. The receptor content in ovary, testis, lung, and spleen was intermediate. The apparent molecular weight of the IGF-II/M6P receptor (220,000 kilos without reduction of disulfide bonds) varied among the different tissues: in brain the receptor was of lower molecular weight than in other organs. Immunoquantitation experiments employing 125I-protein A and protein extracts from human kidney at different ages revealed a small, albeit not significant, difference of the receptor content between fetal and postnatal tissues: as in other species, larger amounts of receptor seemed to be present in fetal than in postnatal organs. In addition, no significant difference of the receptor content between human fetal liver and early postnatal liver was measured employing 125I-protein A-immunoquantitation in three fetal and five postnatal liver tissue samples. The distribution of IGF-binding protein (IGEBP) species, another abundant and major class of IGF binding principles, was also measured in human fetal and early postnatal lung, liver, kidney, muscle, and brain using Western ligand blotting with 125I-IGF-II: as with IGF-II/M6P receptor immunoreactivity there was differential expression of the different classes of IGFBPs in the various organs.(ABSTRACT TRUNCATED AT 400 WORDS)

Cloning of an ovine 11 beta-hydroxysteroid dehydrogenase complementary deoxyribonucleic acid: tissue and temporal distribution of its messenger ribonucleic acid during fetal and neonatal development.

Abstract: Glucocorticoids promote the development of many organ systems vital for extrauterine survival, and fetal cortisol provides the trigger for birth in sheep The activity of glucocorticoids may be influenced at a cellular level by 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), which is responsible for the interconversion of cortisol and cortisone To examine 11 beta-HSD gene expression during fetal development, two overlapping clones which yield a 14 kilobase (kb) complementary DNA encoding sheep 11 beta-HSD from a liver library were isolated by using a rat 11 beta-HSD cDNA as the probe This cDNA contains a 879 base pair open reading frame for a protein of 292 amino acids that has more than 70% sequence identity to rat and human 11 beta-HSDs To define the tissue distribution of 11 beta-HSD messenger RNA in sheep, selected tissues were collected from one fetus at day 130 and term (approximately 145 days), and from a nonpregnant ewe Cellular RNA was extracted and subjected to Northern blot analysis, and a single 18 kb transcript was detected in the fetal and adult liver, lung, hypothalamus, anterior pituitary, and placenta This was undetectable in adrenals and kidneys, but a smaller (15 kb) transcript was present in fetal and adult kidney RNA The relative abundance of 11 beta-HSD mRNA was greatest in fetal and adult livers, and it was much higher in adult liver, lung, and kidney than in the corresponding fetal tissues To examine whether 11 beta-HSD gene expression is developmentally regulated in the fetal sheep, liver, lung, and kidney tissues were taken from fetuses at day 60-70, day 100-110, day 125-130, at term, and from newborn lambs (24-48 h old) In the lung and kidney, the relative abundance of 11 beta-HSD mRNA did not change from day 60 to term but increased in the lungs of newborn lambs In contrast, 11 beta-HSD mRNA levels in the liver increased between day 125 and term and rose further in the newborn Collectively, these results demonstrate that 11 beta-HSD gene expression in sheep is regulated in a tissue-specific and developmentally programmed manner

Prolonged hypoxia induced by the reduction of maternal uterine blood flow alters insulin-like growth factor-binding protein-1 (IGFBP-1) and IGFBP-2 gene expression in the ovine fetus.

Abstract: Insulin-like growth factors (IGF-I and IGF-II) are potent mitogenic and differentiating peptides which are synthesized by many fetal tissues. In the circulation and tissue fluids, IGFs are bound to binding proteins (BPs) which not only function as carrier proteins, but also inhibit or modulate the biological actions of IGFs. We have previously shown that prolonged hypoxia in the ovine fetus induced by the reduction of maternal uterine blood flow for 24 h causes a reduction in the DNA synthesis rate in selected fetal tissues. To determine if this effect is due to alterations in the local synthesis of tissue IGFs and their binding proteins or to changes in systemic concentrations of IGFs and IGFBPs, we have investigated the abundance of mRNAs encoding IGFs and IGFBPs in selected tissues and changes in plasma IGFs and IGFBPs. Ovine fetuses (115-120 days gestation; n = 6) underwent 24 h of hypoxia by the reduction of maternal uterine blood flow (RUBF). Controls (n = 6) underwent the same surgical procedure wi...