Literature DB >> 12194114

Nitrofen inhibition of pulmonary growth and development occurs in the early embryonic mouse.

Michael J Leinwand1, J Denise Tefft, Jingsong Zhao, Colleen Coleman, Kathryn D Anderson, David Warburton.   

Abstract

BACKGROUND/
PURPOSE: It was believed previously that pulmonary hypoplasia in congenital diaphragmatic hernia (CDH) was a consequence of the herniation of abdominal viscera into the chest. Using the murine nitrofen-induced model of CDH, the authors evaluated lung growth and development before diaphragm closure or herniation.
METHODS: The authors examined nitrofen-exposed early embryonic lungs on embryonic day 12 (E12). Branching morphogenesis was quantified before and after 4 days in culture in serumless chemically defined media and compared with age-matched control lungs. The mRNA expression of proliferative and developmental markers in cultured lungs was then determined.
RESULTS: Nitrofen-exposed lungs had 30% fewer total terminal branches than age-matched controls (9.3 +/- 1.9 nitrofen v 13.7 +/- 2.6 control; P <.001). Hypoplasia also was more profound in the left than the right lung. These effects persisted after culturing the lungs for 4 days in serumless chemically-defined media (31.7 +/- 6.8 nitrofen v 42.9 +/- 8.4 control, P <.001). Furthermore, the mRNA expression of proliferative and developmental markers was decreased in nitrofen-exposed E12 lungs cultured for 4 days (as a percentage of age-matched controls): cyclin A (69.28%; P =.04), Nkx2.1 (44.4%, 0.04), SP-A (24.1%; P =.008), SP-B (23.4%; P =.05), SP-C (20%; P =.06), and CC-10 (13.8%; P =.04).
CONCLUSION: Nitrofen induces primary pulmonary hypoplasia and immaturity in the early embryonic mouse, and this effect persists in culture. Copyright 2002, Elsevier Science (USA). All rights reserved.

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Year:  2002        PMID: 12194114     DOI: 10.1053/jpsu.2002.34978

Source DB:  PubMed          Journal:  J Pediatr Surg        ISSN: 0022-3468            Impact factor:   2.545


  6 in total

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