Respiratory and Alimentary Relations in Staged Human Embryos

OʼRahilly, Ronan; Müller, Fabiola

doi:10.1177/000348948409300501

Cited by 122 publications

(37 citation statements)

References 24 publications

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“…Instead, they propose that atresia alone is caused by interruption of the blood supply, while isolated tracheo-esophageal fistula is caused by close proximity of the epithelia of both organs. A similar explanation for the embryologic development of tracheo-esophageal fistula is shared by other authors (O'Rahilly and Mü ller, 1984).…”

Section: Discussionsupporting

confidence: 76%

Timing and embryology of esophageal atresia and tracheo-esophageal fistula

et al. 1997

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Background: The embryology of tracheo-esophageal anomalies is controversial. The development of an adriamycin-treated animal model has enabled improved understanding of the embryogenesis of these anomalies. Using this model, we aimed to describe the events leading to esophageal atresia and tracheo-esophageal fistula.Methods: Timed-pregnant Sprague-Dawley rats were injected daily with adriamycin intraperitoneally at a dose of 2 mg/Kg on days 6-9 of gestation. Histological sections were prepared from 96 experimental and 34 control rat embryos at 11-14 days gestation (plug day ‫؍‬ day 0).Results: The tracheal bud failed to develop normally from the foregut, leaving the foregut to give origin to both bronchi and differentiate into the respiratory system, and then continue as a fistula to the lower esophageal segment. Dorsal pouching of the proximal foregut, which is seen clearly on day 13, is responsible for the development of the upper esophageal segment.Conclusions: We conclude that failure of the tracheal bud to develop normally from the primitive foregut is the main event which leads to the tracheo-esophageal anomalies. As the proximal part of the primitive foregut develops primarily into a trachea rather than an esophagus, the anomaly of the esophagus could be described as agenesis instead of atresia. Anat. Rec. 249:240-248, 1997. Key words: embryology; esophageal atresia; tracheo-esophageal fistula; notochordThe first clinical description of esophageal atresia was by Durston in 1670, while tracheo-esophageal fistula was reported by Gibson in 1697 (Myers, 1991).Despite awareness of these conditions, only recently has it been investigated in embryos. There are many theories regarding the embryogenesis of esophageal atresia but most fail to explain the combination of atresia and fistula. Part of the difficulty has been the lack of a reproducible animal model of esophageal atresia and other tracheo-esophageal anomalies, but now the adriamycin-induced fetal rat model (Thompson et al., 1978;Diez-Pardo et al., 1996;Qi et al., 1996) provides us with a model of esophageal atresia and tracheo-esophageal fistula.By comparing the morphological changes which occur in the treated rats and normal controls, we aimed to determine the embryological deviations that produce esophageal atresia and tracheo-esophageal fistula. MATERIALS AND METHODSTimed-pregnant Sprague-Dawley rats from a colony maintained at the Royal Children's Hospital were used. The day a vaginal plug was found was considered day 0 of gestation. The rats were housed individually in solid-bottom plastic cages on sawdust bedding at a controlled temperature of 21°C and humidity of 55%, with a 12L:12D photoperiod. Standard laboratory chow and water were allowed ad libitum. Treated animals were injected daily with adriamycin (David Bull Laboratories, Melbourne) at a dose of 2 mg/Kg intraperitoneally (i.p.) on days 6-9 of gestation (four injections). Animals were euthanized using carbon dioxide inhalation overdose. Ninety-six experimental and 34 control embryo...

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Section: Discussionsupporting

confidence: 76%

Timing and embryology of esophageal atresia and tracheo-esophageal fistula

et al. 1997

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“…However, there are several further studies in human embryos in the same stage of duodenal development showing that the total duodenal occlusion is not constantly true. So, this theory has been questioned [3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Morphologic study of embryonic development of rat duodenum through a computerized three-dimensional reconstruction: critical analysis of solid core theory

et al. 2008

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To date, intrinsic obstructions of the duodenum have been explained by the "solid core" theory, described by Tandler in 1902 (Morphol Jahrb 29:187-216, 1902). This study aimed to evaluate the epithelial occlusion of rat duodenum during embryonic development, through optical microscopy and computerized three-dimensional reconstruction. The Wistar rat embryos used in this study had 13, 14, 15, and 16 days of gestation. This corresponds to human embryos with 33, 40, 44, and 52 days of development, which is between the fifth and eighth week. The study included 12 embryos studied by optical microscopy, and four by three-dimensional reconstruction (those with 13, 14, 15, and 16 days). Through optical microscopy, an intense epithelial proliferation was observed in the gestation embryo of 13 days, with no occlusion of the opening of the duodenum. In the embryos with 14, 15, and 16 days of gestation, an increase in diameter of the duodenum was observed along with intestinal development. Through three-dimensional reconstruction, it was observed that the opening of the digestive tube of rat embryos with 13-16 days of gestation is never obstructed by epithelial proliferation, although it may follow a sinuous path. This study concludes that the "solid core" phase described by Tandler does not occur in the embryonic development of rat duodenum.

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“…1-3 However, there exists some controversy surrounding its details 4,5 and about the actual existence of the septum itself. 6,7 To understand how the foregut differentiates, verification of the abnormal as well as the normal process would be helpful.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Development of Normal Foregut and Tracheoesophageal Fistula in an Adriamycin Rat Model Using Three-Dimensional Image Reconstruction

2001

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To examine the developmental process of the normal trachea and esophagus and their maldevelopment leading to tracheoesophageal fistula (TEF), we performed three-dimensional (3-D) image reconstruction of the developing foregut in normal and adriamycin (ADM)-induced TEF rats. Microscopic images of serial sections of embryos from seven normal and 14 ADM-treated rats killed every half a day after 11-14 days' gestation were traced and reconstructed using a 3-D construction imaging system (TRI, RATOC System Engineering, Tokyo, Japan). In the normal embryos, the lung bud appeared just below the pharyngeal foregut on day 11 and it elongated caudally to shape into the trachea as they grew. A 'tracheoesophageal septum" did not emerge. In the TEF embryos, although the lung bud appeared in a similar position on day 11, the trachea and esophagus did not separate and only a common foregut tube elongated caudally, then bilateral bronchial primordia emerged directly from it. Furthermore, abnormal development of the notochord was evident, being retarded in separation from the foregut, finally descending along a more ventral course and bending sharply around the level of the bifurcation. Microscopically, less mesenchymal cellularity around the foregut was noted in the TEF embryos. The trachea seemed to be formed only by caudal elongation of the lung bud in the normal embryos. In the ADM-induced TEF embryos, the upper foregut appeared to develop only into the trachea, and this maldevelopment may be implicated in the abnormal interaction between the foregut and the surrounding mesenchyme.

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Respiratory and Alimentary Relations in Staged Human Embryos

Cited by 122 publications

References 24 publications

Timing and embryology of esophageal atresia and tracheo-esophageal fistula

Timing and embryology of esophageal atresia and tracheo-esophageal fistula

Morphologic study of embryonic development of rat duodenum through a computerized three-dimensional reconstruction: critical analysis of solid core theory

Analysis of the Development of Normal Foregut and Tracheoesophageal Fistula in an Adriamycin Rat Model Using Three-Dimensional Image Reconstruction

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