Early gestational intrauterine infection induces postnatal lung inflammation and arrests lung development in a rat model.
OBJECTIVE
In order to investigate the early gestational inflammation effect on the prenatal and postnatal lung development, identification of the proinflammatory cytokines (IL-1β and TNF-α), genes implicated in angiogenesis (Vascular endothelial growth factor [VEGF], fms-like tyrosine kinase-1 [Flt-1], fetal liver kinase-1 [Flk-1]), and surfactant proteins (SPs) were observed.


METHODS
Escherichia coli (E. coli) was inoculated into uterine cervix of pregnant rats at embryonic day 15 (E15) during pseudoglandular period of lung development and the control group was inoculated with normal saline. IL-1β, TNF-α, VEGF, Flt-1, Flk-1, SP-A, and SP-B mRNA in pup's lung at E17, 19, 21 and postnatal day (P) 1, 3, 7, 14 were quantified by real-time RT-PCR. Western blot or immunohistochemistry analysis was also performed for the evaluation of VEGF, Flk-1, Flt-1, and SP-A expression in pup's lung.


RESULTS
Compared with the control group, the fetal lung of the E. coli-treated group was more immature, the postnatal lung development was impaired marked by less alveoli, fewer secondary septa, and thicker alveolar wall. The lung weight and lung/body weight ratio were lower in the E. coli-treated group pups. IL-1β and TNF-α mRNA were increased significantly in E. coli-treated pup's lung after birth, but no significant difference of IL-1β and TNF-α mRNA levels in fetal lung were found between the two groups. SP-A expression was depressed at E17, E19, and E21 after intrauterine E. coli treated, accompanied with lower SP-B mRNA level at E19 and E21. Furthermore, intrauterine E. coli treated reduced the VEGF mRNA and protein levels in the fetal lung at E17 and E19, while the expression of Flt-1 and Flk-1 were higher at P7, P14 and P1, P7, P14, respectively, compared to the controls.


CONCLUSIONS
These results suggested early gestational intrauterine E. coli infection could induce a postnatal pulmonary inflammation and might arrest the alveolarization in developing lung which was involved with the VEGF signaling. However, intrauterine E. coli infection could not induce the increase of proinflammatory cytokines in fetal lung and might fail to accelerate the maturation of fetal lung.
Zhan
Can-Yang
CY
Department of Neonatology, Children's Hospital, Zhejiang University School of Medicine and Zhejiang Key Laboratory for Diagnosis and Therapy of Neonatal Disease, Zhugan Xiang 57, Hangzhou 310003, People's Republic of China.
Yuan
Tian-Ming
TM
Sun
Yi
Y
Yu
Hui-Min
HM
D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000150:complications / Q000196:embryology; D005260:Female; D005333:Fetus / Q000196:embryology / Q000473:pathology; D005865:Gestational Age; D008168:Lung / Q000196:embryology / Q000254:growth & development* / Q000502:physiology; D008171:Lung Diseases / Q000151:congenital / Q000196:embryology / Q000209:etiology; D011014:Pneumonia / Q000151:congenital / Q000196:embryology / Q000209:etiology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014591:Uterine Diseases / Q000150:complications* / Q000196:embryology / Q000276:immunology / Q000473:pathology*