Effects of estrogen on lung development in a rat model of diaphragmatic hernia

J Pediatr Surg. 2010 Dec;45(12):2340-5. doi: 10.1016/j.jpedsurg.2010.08.028.

Abstract

Purpose: The study aimed to observe the influence of estradiol on rat models with congenital diaphragmatic hernia (CDH) and understand the potential mechanism.

Methods: Eleven pregnant female Sprague-Dawley rats were randomly divided into 3 groups on day 9.5 of gestation: group C (n = 2) was administered 2 mL of olive oil, whereas group N (n = 3) and group E (n = 6) were administered 200 mg of nitrofen. Antenatal estradiol was given subcutaneously to group E on days 18.5, 19.5, and 20.5 of gestation. Histologic evaluations, incidence of CDH, and the immunoreactivity of transforming growth factor (TGF)-β1 in lung were observed. In addition, the mRNA levels of TGF-β1, type I TGF-β receptor (TβRI), and type II TGF-β receptor (TβRII) were determined.

Results: Histologically, the lungs of group N fetuses were hypoplastic compared with those of group C and had thick-walled septa with poorly developed saccules. Group E showed improved mesenchymal differentiation with well-developed saccules. There was no significant difference between the incidence of CDH in group N and that in group E. The expression of TGF-β1 in lung tissue and arterioles in group N were significantly higher than those in group C and E. Moreover, relative mRNA expression levels of TGF-β1 and TβRI in group N were markedly higher than those in group C, whereas those in group E were significantly decreased compared with group N.

Conclusions: Estradiol can promote lung development in rats with CDH. The down-regulation of TGF-β1 and its signaling pathway may play a role in this effect.

MeSH terms

  • Animals
  • Arterioles / metabolism
  • Drug Evaluation, Preclinical
  • Estradiol / administration & dosage
  • Estradiol / pharmacology
  • Estradiol / therapeutic use*
  • Female
  • Fetal Organ Maturity / drug effects*
  • Gene Expression Regulation, Developmental / drug effects
  • Hernia, Diaphragmatic / chemically induced
  • Hernia, Diaphragmatic / drug therapy
  • Hernia, Diaphragmatic / embryology*
  • Hernia, Diaphragmatic / metabolism
  • Hernias, Diaphragmatic, Congenital*
  • Injections, Subcutaneous
  • Lung / blood supply
  • Lung / drug effects
  • Lung / embryology*
  • Lung / metabolism
  • Phenyl Ethers / toxicity
  • Pregnancy
  • Protein Serine-Threonine Kinases / biosynthesis
  • Protein Serine-Threonine Kinases / genetics
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / biosynthesis
  • Receptors, Transforming Growth Factor beta / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transforming Growth Factor beta1 / biosynthesis
  • Transforming Growth Factor beta1 / genetics

Substances

  • Phenyl Ethers
  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Estradiol
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • Tgfbr1 protein, rat
  • nitrofen