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Early gestational intrauterine infection induces postnatal lung inflammation and arrests lung development in a rat
Can-Yang Zhan1, Tian-Ming Yuan, Yi Sun
1Department 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.
Insights
Early gestational E. coli infection impairs postnatal lung development by causing inflammation and arresting alveolarization, potentially involving VEGF signaling. Fetal lung maturation was not accelerated, and proinflammatory cytokines did not increase in utero.
Area of Science:
- Reproductive Biology
- Developmental Biology
- Pulmonary Medicine
Background:
- Early gestational inflammation can impact fetal development.
- Intrauterine infections pose risks to prenatal and postnatal health.
- Lung development involves complex molecular and cellular processes.
Purpose of the Study:
- To investigate the effects of early gestational inflammation on prenatal and postnatal lung development.
- To identify the roles of proinflammatory cytokines, angiogenesis genes, and surfactant proteins in this process.
Main Methods:
- Pregnant rats were infected with Escherichia coli (E. coli) or saline at embryonic day 15.
- Gene and protein expression of cytokines, angiogenesis factors, and surfactant proteins were quantified using RT-PCR and Western blot.
- Lung development was assessed morphologically and by organ weight.
Main Results:
- E. coli infection led to immature fetal lungs and impaired postnatal lung development with reduced alveoli and thicker walls.
- Postnatal lung inflammation was observed, with increased IL-1β and TNF-α mRNA.
- Surfactant protein A and B expression was reduced, while VEGF levels decreased in fetal lungs, and angiogenesis markers (Flt-1, Flk-1) increased postnatally.
Conclusions:
- Early gestational E. coli infection induces postnatal pulmonary inflammation and arrests alveolarization, potentially mediated by VEGF signaling.
- Intrauterine infection did not increase fetal lung proinflammatory cytokines or accelerate fetal lung maturation.
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.
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