Abnormal control of lung branching in experimental esophageal atresia

AC Fragoso, R Aras-Lopez, L Martinez… - Pediatric surgery …, 2013 - Springer
AC Fragoso, R Aras-Lopez, L Martinez, J Estevao-Costa, JA Tovar
Pediatric surgery international, 2013Springer
Purpose Esophageal atresia and tracheo-esophageal fistula (EA-TEF) result from abnormal
division of the foregut into esophagus and trachea thus, it may influence airway branching
and lung development. The present study examined lung morphogenesis in fetuses with EA-
TEF focusing in the expression of FGF10 and its receptor FGFR2 IIIb. Methods Pregnant rats
received either 1.75 mg/kg ip adriamycin or vehicle on E7, E8 and E9. Embryos were
recovered at E15, E18 and E21 and lungs processed for immunohistochemistry and RT …
Purpose
Esophageal atresia and tracheo-esophageal fistula (EA-TEF) result from abnormal division of the foregut into esophagus and trachea thus, it may influence airway branching and lung development. The present study examined lung morphogenesis in fetuses with EA-TEF focusing in the expression of FGF10 and its receptor FGFR2 IIIb.
Methods
Pregnant rats received either 1.75 mg/kg i.p. adriamycin or vehicle on E7, E8 and E9. Embryos were recovered at E15, E18 and E21 and lungs processed for immunohistochemistry and RT-PCR. Three groups were studied: control, adriamycin-exposed with EA-TEF, and adriamycin-exposed without EA-TEF. Comparisons were performed with Mann–Whitney or t tests (significance level, 5 %).
Results
Lung weight at E15 and E18 were significantly lower in adriaEA fetuses in which the relative mRNA levels of FGF10 were significantly higher. These differences disappeared near term. The receptor FGFR2 IIIb messenger was only significantly increased in adria noEA fetuses at E15. Immunohistochemical study was consistent with these findings.
Conclusions
Abnormal expression of FGF10 during earlier stages of development, when the lungs are smaller than controls, suggests a compensatory response aimed at “catching up” delayed tracheobronchial branching. Whether similar changes take place in the human condition and influence respiratory physiology remain to be determined.
Springer
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