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Published on: February 8, 2013
Differential effects of vitamin A on fetal lung growth and diaphragmatic formation in nitrofen-induced rat model
T Oshiro1, Y Asato, M Sakanashi
1Department of Pediatrics, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan. k018733@med.u-ryukyu.ac.jp
Insights
Antenatal vitamin A treatment significantly reduced congenital diaphragmatic hernia (CDH) incidence in a rat model. This intervention lowered CDH rates without promoting lung maturation, offering a potential new therapeutic approach.
Area of Science:
- Developmental biology
- Teratology
- Neonatal medicine
Background:
- Congenital diaphragmatic hernia (CDH) leads to high neonatal mortality and morbidity.
- Pulmonary hypoplasia and hypertension are key complications of CDH.
- The role of lung growth in CDH pathogenesis and the efficacy of antenatal interventions require further investigation.
Purpose of the Study:
- To investigate the effect of antenatal vitamin A administration on lung growth and CDH incidence.
- To explore vitamin A's potential as a therapeutic agent for CDH in a preclinical model.
Main Methods:
- A nitrofen-induced rat model was used to study CDH.
- Animals were randomly assigned to control, vitamin A, nitrofen, or nitrofen/vitamin A groups.
- Incidence of CDH, fetal lung weight, body weight, and lung surfactant protein mRNA levels were assessed.
Main Results:
- The nitrofen/vitamin A group showed a reduced CDH incidence (54%) compared to the nitrofen group (85%).
- Fetal lung weight-to-body weight ratio was slightly increased in the nitrofen/vitamin A group versus the nitrofen group.
- mRNA levels of lung surfactant proteins decreased in the nitrofen/vitamin A group.
Conclusions:
- Antenatal vitamin A treatment effectively reduced the incidence of CDH in the nitrofen-induced rat model.
- Vitamin A's protective effect on CDH occurred independently of promoting lung maturation.
- These findings suggest vitamin A as a potential therapeutic strategy for congenital diaphragmatic hernia.
Abstract:
Congenital diaphragmatic hernia (CDH) is associated with high neonatal mortality and morbidity due to pulmonary hypoplasia and pulmonary hypertension. Antenatal interventions have been developed in an attempt to reduce the unacceptable mortality rate of CDH. The pathogenesis of pulmonary hypoplasia is not fully understood. It is not clear whether the increase of lung growth would be necessary for diaphragmatic closure. Vitamin A is important for various aspects of lung development. Therefore, the aim of this study was to examine whether antenatal treatment with vitamin A can increase lung growth and reduce the incidence of CDH in a nitrofen-treated rat model. The animals were randomly assigned to four groups: control, vitamin A, nitrofen, and nitrofen/vitamin A (NIP/Vit A). The incidence of CDH in the NIP/Vit A group (54%) was markedly lower than that in the nitrofen-treated group (85%). Although lung weight was decreased in the nitrofen-treated and NIP/vitamin A groups, the fetal lung weight-to-body weight ratio was slightly increased in the NIP/vitamin A group, compared to the nitrofen-treated group. The mRNA levels of lung surfactant proteins were decreased in the NIP/vitamin A group. We conclude that antenatal treatment with vitamin A reduced the incidence of CDH without lung maturation in the nitrofen-induced rat model.
