Prenatal vitamin E treatment improves lung growth in fetal rats with congenital diaphragmatic hernia

Saleem Islam, Vinod Narra, Gregory M. Coté, Thomas F. Manganaro, Patricia K. Donahoe, Jay J. Schnitzer

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)


Purpose: Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypoplasia. To discover factors that would accelerate fetal lung growth, the authors developed models of hypoplasia, found that antioxidants improved lung growth in vitro, and then proceeded to in vivo studies. Methods: Timed-pregnant rats were fed nitrofen (100 mg) on gestational day 9.5 (term, 22), and fetal lungs were harvested at day 13.5 and placed in organ culture in serum-free media with (n = 10) or without (n = 9) additional vitamin E (0.134 IU/mL). Camera lucida tracings were made daily on live, unstained lungs for 4 days, scanned, digitized, and analyzed for multiple growth parameters. Similar nitrofen-exposed rats were fed an optimized total dose of 150 IU vitamin E (n = 19) or olive oil (n = 13) from days 16.5 to 20.5, and fetal lungs were harvested at day 21.5, weighed and fixed for histology, or homogenized and biochemically analyzed. Results: Vitamin E accelerated hypoplastic fetal lung growth in vitro as measured by area, perimeter, lung bud count, perimeter over square root area, and fractal dimension. In vivo vitamin E significantly increased lung weights, total DNA, and protein contents. Conclusions: Vitamin E accelerates hypoplastic fetal rat lung growth and complexity in vitro, and prenatal vitamin E treatment in vivo improves pulmonary hypoplasia in fetal rats with CDH.

Original languageEnglish
Pages (from-to)172-177
Number of pages6
JournalJournal of Pediatric Surgery
Issue number1
Publication statusPublished - Jan 1999
Externally publishedYes


  • Congenital diaphragmatic hernia
  • Fetal lung organ culture
  • Prenatal vitamin E
  • Pulmonary hypoplasia


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