NEW YORKPrenatal vitamin A deficiency may lead to postnatal airway hyperresponsiveness, known as asthma, according to a study published in the Journal of Clinical Investigation.
According to researchers from Columbia University Medical Center, during the in utero lung forming stage, short-term deficit of the essential vitamin can cause profound changes in the smooth muscle that surrounds the airways, causing adult lungs to respond to environmental or pharmacological stimuli with excessive narrowing of airways.
"Researchers have long wondered what makes some people more susceptible than others to developing asthma symptoms when exposed to the same stimulus," said Wellington V. Cardoso, M.D., Ph.D., senior author, director of the new Columbia Center for Human Development, and a faculty member in the division of pulmonary allergy clinical care medicine. "Our study suggests that the presence of structural and functional abnormalities in the lungs due to vitamin A deficiency during development is an important and underappreciated factor in this susceptibility."
Previous studies were conducted, but until now, little was known about the retinoic acid (RA) deficiency on postnatal airway function.
In an earlier study, Felicia Chen, MD, identified a number of genes regulated by RA signaling in fetal lung development. Additional analysis showed the abnormal presence of genes involved in the formation of smooth muscle when RA signaling was disrupted. This finding prompted the researchers to take a closer look at the effects of vitamin A deficiency on the development of the smooth muscle that surrounds airways as they continued to form and branch.
The vitamin A deficiency was timed to the middle of gestation coinciding with the period of formation of the airway tree in the fetus, Cardos said.
Fetuses that were deprived of vitamin A were found to have excess smooth muscle in the airways, compared with controls. In a subsequent experiment mice were again deprived of vitamin A during the same developmental stage, but returned to a normal diet after that stage and until adulthood.
"When the animals reached adulthood, they appeared normalthat is, they had no problems typically associated with vitamin A deficiency," said Cardoso. "However, pulmonary function tests showed that their lungs were clearly not normal."
The findings underscore the importance of sufficient vitamin A in the diet. More research is necessary to determine how early exposure of the fetus to adverse environmental factors can interfere with crucial developmental mechanisms, Cardoso said.