Sex-specific changes in lung function are associated with the Pald1 gene


Pathological changes in lung function often afflict women harder than men but the mechanisms behind this apparent sex-linkage remain unclear. A new study from IGP reveals a sex-specific correlation between the gene Pald1 and lung function in mice.

Chronic obstructive pulmonary disease (COPD) is a common disease where lung function is gradually impaired. This is caused by destruction of the lung alveoli, which leads to reduced efficiency of oxygen and carbon dioxide transport. Most COPD patients are smokers and but are differences between men and women in the pathology of the disease. For instance, female smokers with early onset COPD have smoked significantly less than their male counterparts.

Researchers have suggested that the formation of blood vessels has a central role for lung diseases such as COPD. The authors of the present study have previously studied the gene Pald1, which is involved in controlling how and when new blood vessels are formed. The new results show that Pald1 can be linked to lung development and function in a sex specific manner.

“To determine the function of Pald1 we have produced mice that lack this specific gene. When we examined the lungs in both females and males we discovered several examples of defective lung tissue and function that were only present in the females. For instance, female mice lacking Pald1 had enlarged spaces between the alveoli as compared to normal mice. This is a type of defect that resembles the ones that occur in COPD,” says Mats Hellström, researcher at IGP, who has led the study.

The researchers also studied the blood vessels in the lungs and saw that female mice lacking Pald1 had fewer endothelial cells, i.e. the cell type that lines the inside of blood vessels. They also found that a larger proportion of endothelial cells had died in female mice without Pald1. In the males, there was no difference in the number of dead endothelial cells between individuals with or without the Pald1 gene.

“Our results show that Pald1 plays a role in lung development and function and specifically for the survival of endothelial cells in females. These are findings that are consistent with the accumulating evidence regarding sex differences and lung biology,” says Mats Hellström.

The results have been published in the journal Nature Scientific Reports and is a collaboration with researcher at Uppsala University, Karolinska Institutet and several German universities and research centres.

More information:
Article in Nature Scientific Reports
Mats Hellström’s research