Talk:Respiratory System - Diaphragm
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Cite this page: Hill, M.A. (2024, June 26) Embryology Respiratory System - Diaphragm. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Respiratory_System_-_Diaphragm |
2012
Congenital diaphragmatic hernia
Orphanet J Rare Dis. 2012 Jan 3;7:1.
Tovar JA. Source Universidad Autonoma de Madrid, Department of Pediatric Surgery, Hospital Universitario La Paz, Madrid, Spain. jatovar.hulp@salud.madrid.org
Abstract
Congenital Diaphragmatic Hernia (CDH) is defined by the presence of an orifice in the diaphragm, more often left and posterolateral that permits the herniation of abdominal contents into the thorax. The lungs are hypoplastic and have abnormal vessels that cause respiratory insufficiency and persistent pulmonary hypertension with high mortality. About one third of cases have cardiovascular malformations and lesser proportions have skeletal, neural, genitourinary, gastrointestinal or other defects. CDH can be a component of Pallister-Killian, Fryns, Ghersoni-Baruch, WAGR, Denys-Drash, Brachman-De Lange, Donnai-Barrow or Wolf-Hirschhorn syndromes. Some chromosomal anomalies involve CDH as well. The incidence is < 5 in 10,000 live-births. The etiology is unknown although clinical, genetic and experimental evidence points to disturbances in the retinoid-signaling pathway during organogenesis. Antenatal diagnosis is often made and this allows prenatal management (open correction of the hernia in the past and reversible fetoscopic tracheal obstruction nowadays) that may be indicated in cases with severe lung hypoplasia and grim prognosis. Treatment after birth requires all the refinements of critical care including extracorporeal membrane oxygenation prior to surgical correction. The best hospital series report 80% survival but it remains around 50% in population-based studies. Chronic respiratory tract disease, neurodevelopmental problems, neurosensorial hearing loss and gastroesophageal reflux are common problems in survivors. Much more research on several aspects of this severe condition is warranted.
PMID 22214468
Congenital diaphragmatic hernia candidate genes derived from embryonic transcriptomes
Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2978-83. Epub 2012 Feb 6.
Russell MK, Longoni M, Wells J, Maalouf FI, Tracy AA, Loscertales M, Ackerman KG, Pober BR, Lage K, Bult CJ, Donahoe PK. Source Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, MA 02114, USA.
Abstract
Congenital diaphragmatic hernia (CDH) is a common (1 in 3,000 live births) major congenital malformation that results in significant morbidity and mortality. The discovery of CDH loci using standard genetic approaches has been hindered by its genetic heterogeneity. We hypothesized that gene expression profiling of developing embryonic diaphragms would help identify genes likely to be associated with diaphragm defects. We generated a time series of whole-transcriptome expression profiles from laser captured embryonic mouse diaphragms at embryonic day (E)11.5 and E12.5 when experimental perturbations lead to CDH phenotypes, and E16.5 when the diaphragm is fully formed. Gene sets defining biologically relevant pathways and temporal expression trends were identified by using a series of bioinformatic algorithms. These developmental sets were then compared with a manually curated list of genes previously shown to cause diaphragm defects in humans and in mouse models. Our integrative filtering strategy identified 27 candidates for CDH. We examined the diaphragms of knockout mice for one of the candidate genes, pre-B-cell leukemia transcription factor 1 (Pbx1), and identified a range of previously undetected diaphragmatic defects. Our study demonstrates the utility of genetic characterization of normal development as an integral part of a disease gene identification and prioritization strategy for CDH, an approach that can be extended to other diseases and developmental anomalies.
PMID 22315423
2011
Pleuroperitoneal canal closure and the fetal adrenal gland
Anat Rec (Hoboken). 2011 Apr;294(4):633-44. doi: 10.1002/ar.21351. Epub 2011 Mar 2.
Hayashi S, Fukuzawa Y, Rodríguez-Vázquez JF, Cho BH, Verdugo-López S, Murakami G, Nakano T. Source Medical Education Center, Aichi Medical University School of Medicine, Nagakute, Japan. shogo@aichi-med-u.ac.jp
Abstract
Pleuroperitoneal canal (PP canal) closure is generally considered to result from an increase in the height, and subsequent fusion, of the bilateral pleuroperitoneal folds (PP folds). However, the folds develop in the area ventral to the adrenal, in contrast to the final position of the diaphragm, which extends to the dorsal side of the adrenal (the "retro-adrenal" diaphragm). We examined the semiserial histology of 20 human embryos and fetuses (crown-rump length 11-40 mm). We started observations of the canal at the stage through which the lung bud extends far caudally along the dorsal body wall to the level of the future adrenal, and the phrenic nerve has already reached the PP fold. Subsequently, the developing adrenal causes narrowing of the dorsocaudal parts of the canal, and provides the bilateral midsagittal recesses or "false" bottoms of the pleural cavity. However, at this stage, the PP fold mesenchymal cells are still restricted to the ventral side of the adrenal, especially along the liver and esophagus. Thereafter, in accordance with ascent of the lung, possibly due to anchoring of the liver to the adrenal, the PP fold mesenchymal cells seem to migrate laterally along the coelomic mesothelium covering some sheet-like loose mesenchymal tissue behind the adrenal. Final closure of the PP canal by lateral migration to provide the "retro-adrenal" diaphragm is a process quite different from the common dogma. It is likely that the sheet-like loose mesenchymal tissue becomes the caudal part of the pleural cavity through a process involving cell death. Copyright © 2011 Wiley-Liss, Inc.
PMID 21370493
2010
Early development of the primordial mammalian diaphragm and cellular mechanisms of nitrofen-induced congenital diaphragmatic hernia
Birth Defects Res A Clin Mol Teratol. 2010 Jan;88(1):15-24.
Clugston RD, Zhang W, Greer JJ. Source Department of Physiology, University of Alberta, Edmonton, Canada.
Abstract
Congenital diaphragmatic hernia (CDH) is a frequently occurring cause of neonatal respiratory distress and is associated with high mortality and long-term morbidity. Evidence from animal models suggests that CDH has its origins in the malformation of the pleuroperitoneal fold (PPF), a key structure in embryonic diaphragm formation. The aims of this study were to characterize the embryogenesis of the PPF in rats and humans, and to determine the potential mechanism that leads to abnormal PPF development in the nitrofen model of CDH. Analysis of rat embryos, and archived human embryo sections, allowed the timeframe of PPF formation to be determined for both species, thus delineating a critical period of diaphragm development in relation to CDH. Experiments on nitrofen-exposed NIH 3T3 cells in vitro led us to hypothesize that nitrofen might cause diaphragmatic hernia in vivo by two possible mechanisms: through decreased cell proliferation or by inducing apoptosis. Data from nitrofen-exposed rat embryos indicates that the primary mechanism of nitrofen teratogenesis in the PPF is through decreased cell proliferation. This study provides novel insight into the embryogenesis of the PPF in rats and humans, and it indicates that impaired cell proliferation might contribute to abnormal diaphragm development in the nitrofen model of CDH. Copyright 2009 Wiley-Liss, Inc.
PMID 19711422
