RESUMEN
OBJECTIVE: To document the expression of oncofetal antigens and steroid receptors in first trimester human fetal ovaries and to determine the effect of advancing gestation on expression patterns. METHODS: Fetal gonads were collected from surgical terminations of pregnancy, and fetal sex was determined by fluorescence in situ hybridization. Immunocytochemical analysis was performed on paraffin sections of microdissected fetal ovaries using antibodies to carcinoembryonic antigen (CEA), placental alkaline phosphatase (PLAP), hCG, alpha fetoprotein (AFP), CA 125, estrogen receptor (ER) and progesterone receptor (PR) in 12 first trimester human fetal ovaries. Expression was quantified objectively by measuring percentage area of immunoreactivity (PAI) on whole sections of the ovary using an interactive image analysis system. Two pathologists, blinded to the antibodies used, independently viewed and scored all sections. RESULTS: PLAP, PR, ER and CEA were expressed in all 12 ovaries (31%, 28%, 21%, and 16% mean PAI, respectively). A diffuse staining pattern was observed at 8 weeks' gestation, which was more focal and confined to the cortical regions of the gonad by 12 weeks' gestation. Putative primordial germ cells were positive for PLAP, PR and ER but rarely for CEA. The expression (PAI) of PLAP and PR was unchanged during the first trimester, whereas that of ER decreased from 28% to 12%. The expression of CEA and hCG decreased from 8 to 11 weeks and then increased markedly by 13 weeks. AFP had a medullary distribution and was expressed in nine of 12 ovaries (mean PAI 18%). CA 125 expression was minimal or undetected. CONCLUSION: PLAP, ER and PR were the most extensively expressed protein antigens, particularly in fetal ovarian cortex. These variable patterns of expression suggest levels of differentiation in the immature first trimester human fetal ovary.
Asunto(s)
Antígenos de Neoplasias/biosíntesis , Ovario/embriología , Primer Trimestre del Embarazo , Receptores de Esteroides/biosíntesis , Fosfatasa Alcalina/análisis , Biomarcadores de Tumor/biosíntesis , Antígeno Ca-125/análisis , Antígeno Carcinoembrionario/análisis , Gonadotropina Coriónica/análisis , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Embarazo , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Análisis para Determinación del Sexo , alfa-Fetoproteínas/análisisRESUMEN
The developing biliary system in normal human embryos from 29 days to 8 weeks post-fertilization was studied. The primitive extrahepatic bile duct that originates from the embryonic hepatic foregut diverticulum is in contact with the hepatic anlage from the start of organogenesis and remains so throughout the gestational ages examined. The primitive extrahepatic bile duct maintains continuity with the ductal plate from which intrahepatic bile ducts are eventually formed. Contrary to long-held concepts of biliary development, no 'solid stage' of entodermal occlusion of the common bile duct lumen was found at any stage of gestation in the material investigated. Therefore, biliary atresia is not caused by incomplete vacuolization of the 'solid stage'.
Asunto(s)
Conductos Biliares Extrahepáticos/embriología , Conductos Biliares Intrahepáticos/embriología , Atresia Biliar/embriología , Hígado/embriología , Adulto , Conducto Colédoco/embriología , Desarrollo Embrionario y Fetal , Femenino , Feto/embriología , Vesícula Biliar/embriología , Edad Gestacional , Humanos , Inmunohistoquímica , Queratinas/análisis , Hígado/química , Hígado/citología , Conductos Pancreáticos/embriología , EmbarazoRESUMEN
In biliary atresia, inflammation and destruction of extrahepatic and intrahepatic bile ducts with eventual fibrous obliteration occurs, causing neonatal obstructive jaundice. The onset of the disorder may start antenatally and progress after birth, and the porta hepatis is a constant site of involvement. To date, little is known about the intrauterine development of the bile ducts at the porta hepatis. The present work gives an account of the developmental pattern of bile ducts at the level of the porta hepatis in the normal human fetus from the 11th to the 25th weeks of gestation. It has been observed that the proximal portion of the hilar bile ducts derives from the intrahepatic biliary ductal plate. This occurs following a predictable remodeling sequence by which, from many ductal plate-derived ductules, those destined to become definitive bile ducts are enveloped in a concentric cuff of mesenchyma. Those which are not are deleted. The distal portions of the right and left main hepatic ducts develop from the extrahepatic bile duct. There was no gestational period in which the extrahepatic bile duct and the intrahepatic biliary system were separated. Furthermore, the developing intrahepatic bile ducts maintain luminal continuity with the common bile duct from the start of organogenesis. Biliary atresia may result from: (i) failure to establish a definitive type of bile duct; (ii) leakage of bile from primitive bile ducts resulting in an interstitial inflammatory reaction in the adjacent mesenchyma; and (iii) continuous proliferation of primitive bile ducts at the level of the porta hepatis beyond the 25th week of gestation, as a failed compensatory mechanism.
Asunto(s)
Conductos Biliares Extrahepáticos/embriología , Conductos Biliares Intrahepáticos/embriología , Atresia Biliar/embriología , Hígado/embriología , Adulto , Conducto Colédoco/embriología , Desarrollo Embrionario y Fetal , Epitelio/embriología , Femenino , Feto/embriología , Edad Gestacional , Humanos , Inmunohistoquímica , Queratinas/análisis , Hígado/química , EmbarazoRESUMEN
Biliary atresia is an obliterative disorder of the bile ducts, causing obstructive jaundice in neonates. In this study, the developing biliary system of normal human embryos and fetuses was examined and compared with the resected extrahepatic biliary remnants from 205 cases of biliary atresia. At the porta hepatis level, it was found that the primary biliary ductal plate undergoes a specific sequence of remodelling, resulting in the formation of large tubular bile ducts surrounded by thick mesenchyme, between 11 and 13 weeks postfertilisation. These developing ducts are in luminal continuity with the extrahepatic biliary tree throughout gestation. Contrary to long-held belief, no "solid phase" was observed in the development of the extrahepatic bile duct. Examination of the biliary remnants in biliary atresia showed that the porta hepatis is encased in fibrous tissue, and a variable pattern of obliteration of the common hepatic and common bile ducts was observed. Anticytokeratin immunostaining showed similarities between the abnormal ductules within the porta hepatis in biliary atresia, and the developing bile ducts in the first trimester. Biliary atresia may be caused by failure of the remodelling process at the hepatic hilum, with persistence of fetal bile ducts poorly supported by mesenchyme. As bile flow increases perinatally, bile leakage from these abnormal ducts may trigger an intense inflammatory reaction, with subsequent obliteration of the biliary tree.
Asunto(s)
Conductos Biliares Extrahepáticos/embriología , Atresia Biliar/embriología , Conductos Biliares Extrahepáticos/anomalías , Conductos Biliares Extrahepáticos/química , Atresia Biliar/metabolismo , Edad Gestacional , Humanos , Inmunohistoquímica , Queratinas/análisisRESUMEN
The aim of the present investigation was to study the developing peptidergic innervation of the human fetal heart of 7-24 wk gestational age. An immunohistochemical approach was adopted and the total innervation visualised with antisera to general neuronal and Schwann cell markers, while the onset and development of specific neuropeptide-containing subpopulations were investigated using antisera to neuropeptide Y (NPY), somatostatin, vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and substance P (SP). Cardiac ganglia and nerves were demonstrated from 7 wk of gestation whereas peptide-immunoreactive nerves were not observed until the 10th week of gestation. NPY-immunoreactive nerve fibres constituted the major subpopulation of peptide-containing nerves identified in the fetal heart, exhibiting a descending atrial to ventricular density gradient, and were first identified during the 10th wk of gestation. Somatostatin- and VIP-immunoreactive nerves appeared at 10-12 wk of gestation and were mainly distributed in the atria. Somatostatin immunoreactivity was localised to cell bodies in cardiac ganglia, as well as to nerve fibres, indicating an intrinsic origin for this nerve subpopulation. Conversely, the other peptide-containing nerves appear to be of extrinsic origin, including those immunoreactive for VIP. Intracardiac neurons exhibit a transient expression of tyrosine hydroxylase immunoreactivity. Putative sympathetic nerve fibres, displaying tyrosine hydroxylase and NPY immunoreactivity, were demonstrated before the adrenergic innervation has previously been shown to be present by formaldehyde-induced fluorescence staining of catecholamines. The onset of the CGRP- and SP-immunoreactive innervation, at 18-24 wk of gestation, followed the appearance of other peptide-containing nerves, suggesting that the sensory, afferent innervation occurs later than the autonomic. The differential appearance and distribution of peptide-containing nerve subpopulations indicate that there is a chronological order to the development of the autonomic and sensory components of human cardiac innervation.
Asunto(s)
Corazón Fetal/inervación , Neuropéptidos/análisis , Péptido Relacionado con Gen de Calcitonina/análisis , Corazón Fetal/química , Corazón Fetal/enzimología , Técnica del Anticuerpo Fluorescente , Edad Gestacional , Humanos , Neuronas/química , Neuropéptido Y/análisis , Somatostatina/análisis , Sustancia P/análisis , Tirosina 3-Monooxigenasa/metabolismo , Péptido Intestinal Vasoactivo/análisisRESUMEN
The placentae of 46 normal pregnancies artificially terminated between 6 and 15 weeks of gestation were investigated morphologically to provide trends in early villous development. Study of the specimens included phase contrast microscopic examination and histomorphometric investigation in all cases, and scanning electron microscopy in ten cases. Histomorphometric measurements included the villous barrier thickness i.e. the distance between the intervillous space and the villous capillary lumen, the trophoblastic layer thickness and the volume fraction of each villous constituents, i.e. trophoblast, stroma and capillaries. Significant negative correlations were observed between gestational age and the villous barrier and trophoblastic thickness. The data obtained were separated into two groups, embryonic (5-10 weeks) and fetal (11-15 weeks) groups, and compared. The mean barrier thickness, the mean trophoblastic thickness, the mean volume fraction for trophoblast and the sprouting-villous index were significantly greater during the embryonic period compared with the fetal period. The mean volume fraction for the stroma and for the fetal capillaries, and the mean number of capillary profiles per villous profile were significantly smaller during the embryonic period than during the fetal period. The comparison of placental histomorphometric data obtained in cases of normal early pregnancies with those observed in cases of abnormal early pregnancies could help us to elucidate the origin of anatomical and biological changes in these cases.
Asunto(s)
Vellosidades Coriónicas/embriología , Análisis de Varianza , Vellosidades Coriónicas/anatomía & histología , Vellosidades Coriónicas/irrigación sanguínea , Desarrollo Embrionario y Fetal , Femenino , Edad Gestacional , Humanos , Microscopía de Contraste de Fase , Embarazo , Primer Trimestre del Embarazo , Análisis de Regresión , Trofoblastos/fisiologíaRESUMEN
Segmental imaging studies of the respiratory epithelium from human embryos and fetuses of normal karyotype have demonstrated that ciliogenesis and ciliation of the respiratory epithelium starts at 7 weeks of gestation. Ciliated cell differentiation follows a pre-determined pattern of distribution. It starts exclusively in the upper segment of the membranous trachea and spreads distally. Ciliation of the carinal angle takes place at 8 weeks of gestation. Three patterns of basal body formation were identified. The various morphological features encountered are described and compared with those observed in cases of Immotile Cilia Syndrome and other pathological conditions. Ciliation of the respiratory epithelium in the cartilaginous trachea does not take place until after the 12th week of gestation. The morphological findings identified in our case material are in agreement with those observed in the developing respiratory epithelium of other higher mammals.
Asunto(s)
Desarrollo Embrionario y Fetal , Sistema Respiratorio/ultraestructura , Bronquios/embriología , Bronquios/ultraestructura , Cilios/ultraestructura , Epitelio/ultraestructura , Femenino , Humanos , Microscopía Electrónica , Microscopía Electrónica de Rastreo , Embarazo , Primer Trimestre del Embarazo , Fenómenos Fisiológicos Respiratorios , Sistema Respiratorio/embriología , Tráquea/embriología , Tráquea/ultraestructuraRESUMEN
Pathological changes identified in the muscular wall of the stomach from two young insulin-dependent diabetic patients suffering from severe gastric autonomic neuropathy are presented. Scattered smooth muscle cells appearing as homogeneous round eosinophilic bodies ("M" bodies) among areas of sub-total smooth muscle cell atrophy together with intercellular collagen proliferation were identified in the muscularis propria of the stomach. Ultrastructurally, the "M" bodies are transformed smooth muscle cells undergoing a form of necrobiosis with peculiar intracellular features. These changes appear characteristic of end-stage diabetic gastric autonomic neuropathy when compared with other pathological conditions involving the gastric wall. The degree and extent of involvement of the various components of the gastric wall are discussed.