The mouse study, published in the Journal of Clinical Investigation, provides evidence that a lack of vitamin A during pregnancy is linked to postnatal airway hyperresponsiveness, which is a hallmark of asthma.
Led by Dr Wellington Cardoso from Columbia University Medical Center (CUMC) in the US, the team's findings show that a short-term deficit of the essential vitamin in pregnancy - and specifically while the lung is forming - is linked to 'profound' changes in the smooth muscle that surrounds the airways of offspring, causing the 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," explained Cardoso. "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."
"More generally, our findings highlight a point often overlooked in adult medicine, which is that adverse foetal exposures that cause subtle changes in developing organs can have lifelong consequences," he added.
The team used a mouse model in which they could control when and in what amount vitamin A would reach the developing foetus through maternal diet.
"We timed the vitamin A deficiency to the middle of gestation, coinciding with the period of formation of the airway tree in the foetus," said Cardoso - noting that foetuses that were deprived of vitamin A were found to have excess smooth muscle in the airways, compared with controls.
In a further 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 normal—that is, they had no problems typically associated with vitamin A deficiency," explained Cardoso. "However, pulmonary function tests showed that their lungs were clearly not normal."
Indeed, when the mice were challenged with methacholine, a chemical that causes the airway to contract, their response was significantly more severe than that of controls, said the team.
Finally, the study showed that the structural and functional changes in the airways occurred in the absence of inflammation.
"This does not imply that inflammation is not an important component of pulmonary conditions characterised by hyperresponsiveness, such as asthma," said Cardoso. "But it reminds us of the multifactor origin of asthma and indicates an additional, structural component that cannot be overlooked."
He said that the findings underscore the importance of sufficient vitamin A in the diet, which remains a significant challenge in developing countries, and in the developed world.
"Most pregnant women in the U.S. are probably getting enough vitamin A in their diet, but it's possible that their babies are not making proper use of it," suggested the lead researcher. "The body has a very complex system for processing vitamin A, and this system is prone to interference from outside factors, such as cigarette smoke and alcohol."
"We need to understand more precisely how early exposures of the foetus to adverse environmental factors can interfere with crucial developmental mechanisms, such as the one we found linking vitamin A to airway structure and function."
Source: Journal of Clinical Investigation
Volume 124, Issue 2, Pages 801–811, doi: 10.1172/JCI70291
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