Genes in Male Chromosome May Protect Against Pulmonary Hypertension, Mouse Study Suggests

A study in mice offers insight into why women are more susceptible to developing pulmonary hypertension than men.

It suggests that genes in the Y chromosome – which confers the male sex – may protect against the development of pulmonary hypertension.

The finding suggests that differences in susceptibility to the disease can be found in sex chromosomes as well as sex hormones.

The study, “The Y Chromosome Plays a Protective Role in Experimental Hypoxic Pulmonary Hypertension,” was published in the American Journal of Respiratory and Critical Care Medicine.

Pulmonary hypertension is a chronic disease that affects young women the most. Previous studies have suggested that sex hormones influence the development of pulmonary hypertension.

A team at the University of California, Los Angeles decided to see whether sex chromosomes play a role in the development of pulmonary hypertension in the absence of sex hormones.

Women are born with two X chromosomes, while men carry one X and one Y chromosome.

The UCLA researchers genetically engineered mice to have different combinations of sex chromosomes, according to a news release. Then they looked at whether the mice would develop the disease.

They put the animals in a low-oxygen environment to trigger pulmonary hypertension. Normal air is 21 percent oxygen. The air the researchers used was 10 percent oxygen.

The scientists engineered one group of mice to carry sex chromosomes independently of their genitalia. A second group was engineered to carry varying numbers of X chromosomes but only one Y chromosome.

To rule out the possibility that sex hormones would affect the research, the researchers removed their sex organs.

After three weeks in the low-oxygen environment, the mice were euthanized so researchers could study their hearts and lungs. They discovered that pulmonary hypertension was less severe in mice with a Y chromosome. Also, while the disease continued to develop in mice lacking a Y chromosome, the development stopped in those with the chromosome.

The findings suggested that genes in the Y chromosome may protect against pulmonary hypertension. Identifying the genes can help researchers better understand the mechanisms underlying the development of pulmonary hypertension and open new paths to therapies.