[Effects of dexamethasone on lung morphogenesis in rats and the expression of Wnt signal transduction pathway in the lung of offspring].
OBJECTIVE
Multiple signal transduction pathways, for example, Wnt signal transduction pathway, fibroblast growth factor (FGF), bone morphogenetic protein (BMP) etc, are involved in rat fetal lung development. Wnt signal has been shown to play important roles in regulating cell differentiation and proliferation. It is demonstrated that antenatal dexamethasone (DEX) use can induce lung dysplasia. A rat premature delivery model was developed in this study to compare the effects of DEX on antenatal rat fetal lung morphogenesis and the expressions of Wnt7b, beta-catenin and glycogen synthase kinase 3beta (GSK-3beta) genes in the lung of offspring on 19th day of embryo.


METHODS
Twelve pregnant rats were divided into three groups randomly: small dose DEX group, large dose DEX group and control group with 4 rats in each group. The rats in the control group were injected with saline 0.5 ml/d; those in small dose DEX group were injected with DEX 0.4 mg/(kg.d), the rats in large dose DEX group were injected with DEX 0.8 mg/(kg.d), DEX was diluted to 0.5 ml by saline. On the 19th day of gestation, the fetuses were surgically taken out and the histologic structures of fetal rat lungs were observed with light microscope. The RT-PCR and Western-blot methods were used to detect the expressions of Wnt7b, GSK-3beta and beta-catenin genes mRNA and protein.


RESULTS
(1) Changes of histologic structure included alveolar numbers: small dose DEX group (15.6 +/- 2.1), large dose DEX group (13.2 +/- 1.6), control group (20.8 +/- 2.0); thickness of alveolar septum: small dose DEX group (11 +/- 5) microm, large dose DEX group (11 +/- 4) microm, control group (13 +/- 7) microm; alveolar space: small dose DEX group (2483 +/- 1336) microm2, large dose DEX group (2924 +/- 1705) microm(2), and control group (1913 +/- 764) microm(2). All the parameters showed significant difference between DEX groups and control group. (P < 0.01 for all comparisons). (2) The expressions of Wnt7b (0.55 +/- 0.19, 0.64 +/- 0.54) and beta-catenin (2.03 +/- 0.58, 2.40 +/- 0.89) genes mRNA of the study groups were significantly higher as compared with those of the control group [Wnt7b (0.18 +/- 0.10), beta-catenin (1.77 +/- 0.54)] (P < 0. 05 for all comparisons) while the expressions of GSK-3beta (1.0 +/- 0.5) were lower than those of the control group (1.1 +/- 0.6) (P < 0. 05). The expressions of GSK-3beta protein in cytoplasm of the study groups [(26.6 +/- 19.7) microg, (10.7 +/- 7.4)microg] reduced gradually while beta-catenin's [(79.5 +/- 1.2) microg, (148.3 +/- 30.4) microg] in the nucleus enhanced simultaneously compared with the control group [(50.0 +/- 00.0) microg ].


CONCLUSIONS
Small dose of antenatal DEX usage can improve the fetal lung development, larger dose of DEX may have negative effect on rat fetal lung morphogenesis. Antenatal DEX usage can change the expressions of Wnt7b, GSK-3beta and beta-catenin genes mRNA and protein, these changes may result in paramorphia during pregnancy.
Wang
Quan
Q
Department of Respiratory Diseases, Nanjing Children's Hospital, Nanjing Medical University, Nanjing 210008, China.
Zhao
De-yu
DY
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D051153:Wnt Proteins / Q000378:metabolism*
D051153:Wnt Proteins; D003907:Dexamethasone