Effects of estrogen on lung development in a rat model of diaphragmatic hernia.
OBJECTIVE
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.
Department of Surgery, Children's Hospital, Fudan University, Shanghai 201102, PR China.
Gong
G
Chen
Yinli
Y
Qiao
Xianmin
X
Xiao
Shan
S
Zheng
Lian
L
Chen
D000818:Animals; D001160:Arterioles / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005325:Fetal Organ Maturity / Q000187:drug effects*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006548:Hernia, Diaphragmatic / Q000139:chemically induced / Q000188:drug therapy / Q000196:embryology* / Q000378:metabolism; D065630:Hernias, Diaphragmatic, Congenital; D007279:Injections, Subcutaneous; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D010647:Phenyl Ethers / Q000633:toxicity; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics
D010647:Phenyl Ethers; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D004958:Estradiol; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625843:Tgfbr1 protein, rat; C007350:nitrofen