Abstract
In recent years, a substantial research effort within the specialty of pediatric surgery has been devoted to improving our knowledge of the natural history and pathophysiology of congenital diaphragmatic hernias (CDH) and pulmonary hypoplasia (PH). However, the embryological background has remained elusive because certain events of normal diaphragmatic development were still unclear and appropriate animal models were lacking. Most authors assume that delayed or inhibited closure of the diaphragm will result in a diaphragmatic defect that is wide enough to allow herniation of the gut into the fetal thoracic cavity. However, we feel that this assumption is not based on appropriate embryological observations. To clarify whether it was correct, we restudied the morphology of pleuroperitoneal openings in normal rat embryos. Shortly before, a model for CDH and PH had been established in rats using nitrofen (2,4-di-chloro-phenyl-p-nitrophenyl ether) as teratogen. We used this model in an attempt to answer the following questions: (1) When does the diaphragmatic defect appear? (2) Are the pleuroperitoneal canals the precursors of the diaphragmatic defect? (3) Why is the lung hypoplastic in babies and infants with CDH?
In our study we made following observations: (1) The typical findings of CDH and PH cannot be explained by inhibited closure of the pleuroperitoneal “canals”. In normal development, the pleuroperitoneal openings are always too small to allow herniation of gut into the thoracic cavity. (2) The maldevelopment of the diaphragm starts rather early in the embryonic period (5th week). The lungs of CDH rats are significantly smaller than those of control rats at the end of the embryonic period (8th week). (3) The maldevelopment of the lungs in rats with CDH is “secondary” to the defect of the diaphragm. (4) The defect of the lungs is “structural” rather than “functional”. Complete spontaneous correction of these lung defects is unlikely even after fetal intervention. (5) The “fetal lamb model” does not completely mimic the full picture of CDH, because the onset of the defect lies clearly in the fetal period. We believe that our rat model is better. It is especially useful for describing the abnormal embryology of this lesion.
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Adzick NS, Outwater KM, Harrison MR, Davies P, Glick PL, de Lorimier AA, Reid LM (1985) Correction of congenital diaphragmatic hernia in utero. IV. An early gestational fetal lamb model for pulmonary vascular morphometric analysis. J Pediatr Surg 20: 73–680
Areechon W, Reid L (1963) Hypoplasia of the lung with congenital diaphragmatic hernia. Br Med J I: 230–233
Bremer JL (1943) The diaphragm and diaphragmatic hernia. Arch Pathol 36: 539–549
Broman I (1902) Über die Entwicklung des Zwerchfells beim Menschen. Verh Anat Ges 16: 9–17
Davies G, Reid L (1970) Growth of the alveoli and pulmonary arteries in childhood. Thorax 25: 669–681
de Lorimier AA, Tierney DF, Parker HR (1967) Hypoplastic lungs in fetal lambs with surgically produced congenital diaphragmatic hernia. Surgery 62: 12–17
de Lorimier AA, Manus AG, Tyler WS (1969) Morphometry of normal and hypoplastic lungs in newborn lambs. Curr Top Surg Res 1: 431–442
Gray SW, Skandalakis JE (1972) Embryology for surgeons. WB Saunders, Philadelphia, pp 359–385
Grosser O, Ortmann R (1970) Grundriß der Entwicklungsgeschichte des Menschen, 7th edn. Springer Berlin Heidelberg New York, pp 124–127
Haller JA Jr, Signer RD, Golladay ES, Inon AE, Harrington DP, Shermeta DW (1976) Pulmonary and ductal hemodynamics in studies of simulated diaphragmatic hernia of fetal and newborn lambs. J Pediatr Surg 11: 675–680
Harrison MR, Jester JA, Ross NA (1980) Correction of congenital diaphragmatic hernia in utero. I. The model: intrathoracic balloon produces fatal pulmonary hypoplasia. Surgery 88: 174–182
Harrison MR, Bressack MA, Churg AM (1980) Correction of congenital diaphragmatic hernia in utero. II. Simulated correction permits fetal lung growth with survival at birth. Surgery 88: 260–268
Harrison MR, Ross NA, de Lorimier AA (1981) Correction of congenital diaphragmatic hernia in utero. III. Development of a successful surgical technique using abdominoplasty to avoid compromise of umbilical blood flow. J Pediatr Surg 16: 934–942
Harrison MR (1989) Fetal diaphragmatic hernia. In: Puri P (ed) Congenital diaphragmatic hernia. Modern problems in paediatrics. Karger, Basel, pp 130–142
Harrison MR (1990) The fetus with a diaphragmatic hernia: pathophysiology, natural history, and surgical management. In: Harrison MR, Golbus MS, Filly RA (eds) The unborn patient. Fetal diagnosis and treatment, 2nd edn. WB Saunders, Philadelphia, pp 295–319
Hashimoto EG, Pringle KC, Soper RT, Brown CK (1985) The creation and repair of diaphragmatic hernia in fetal lambs: morphology of the type II alveolar cell. J Pediatr Surg 20: 354–356
Iritani I (1984) Experimental study on embryogenesis of congenital diaphragmatic hernia. Anat Embryol 169: 133–139
Kent GM, Olley PM, Creighton RE, Dobbinson T, Bryan MH, Symchych P, Zingg W, Cummings JN (1972) Hemodynamic and pulmonary changes following surgical creation of a diaphragmatic hernia in fetal lambs. Surgery 72: 427–433
Kluth D, Petersen C, Zimmermann HJ (1987) The developmental anatomy of congenital diaphragmatic hernia. Pediatr Surg Int 2: 322–326
Kluth D, Petersen C, Zimmermann HJ, Mühlhaus K (1989) The embryology of congenital diaphragmatic hernia. In: Puri P (ed) Congenital diaphragmatic hernia. Modern problems in paediatrics. Karger, Basel, pp 7–21
Kluth D, Kangah R, Reich P, et al. (1990) Nitrofen-induced diaphragmatic hernia in rats: An animal model. J Pediatr Surg 25: 850–854
Moore KL (19855) Körperhöhlen, Mesenterien, Zwerchfell. In: Embryologie, Lehrbuch und Atlas der Entwicklungsgeschichte des Menschen, 2nd ed. Schattauer, Stuttgart, pp 189–201
Nakao Y (1983) Establishment of animal models for congenital diaphragmatic hernia and its pathogenesis. J Nagoya City Univ Med Assoc 34: 318–339
Nakao Y, Ueki R, Nakao Y, Furikawa M, Nomura M, Tada T, Miki M, Kishimoto H (1986) Teratogenic effects of maternal exposure to nitrofen in mice: relationship between congenital diaphragmatic hernia and other congenital anomalies. Nagoya Med J 31: 115–125
O'Rahilly R, Muller F (1984) Chevalier Jackson Lecture. Respiratory and alimentary relations in staged human embryos. New embryological data and congenital anomalies. Ann Otol Rhinol Laryngol 93: 421–429
Patten BM (1965) Human embryology. McGraw-Hill, New York, pp 499–523
Starck D (1975) Embryologie, 3rd edn. Thieme, Stuttgart, pp 488–500
Streeter GL (1945) Descriptions of age group XIII, embryos 4 or 5 mm long, and age group XIV, period of indentation of the lens vesicle. Contrib Embryol Carnegie Inst 31: 27–64
Tenbrinck R, Tibboel D, Gaillard JLJ, et al. (1990) Experimentally induced congenital diaphragmatic hernia in rats. J Pediatr Surg 25: 426–429
Ueki R, Nakao Y, Nishida T, Nakao Y, Wakabayashi T (1990) Lung hypoplasia in developing mice and rats induced by maternal exposure to nitrofen. Cong Anom 30: 133–143
Wells LJ (1954) Development of the human diaphragm and pleural sacs. Contrib Embryol Carnegie Inst 35: 107–137
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Supported in part by “Werner Otto Stiftung”, Hamburg, Germany
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Kluth, D., Tander, B., von Ekesparre, M. et al. Congenital diaphragmatic hernia: the impact of embryological studies. Pediatr Surg Int 10, 16–22 (1995). https://doi.org/10.1007/BF00174435
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DOI: https://doi.org/10.1007/BF00174435