Giving a whole new meaning to "pregnancy brain," a new study shows that male DNA—likely left over from pregnancy with a male fetus—can persist in a woman's brain throughout her life. Although the biological impact of this foreign DNA is unclear, the study also found that women with more male DNA in their brains were less likely to have suffered from Alzheimer's disease—hinting that the male DNA could help protect the mothers from the disease, the researchers say.
During mammalian pregnancy, the mother and fetus exchange DNA and cells. Previous work has shown that fetal cells can linger in the mother's blood and bone for decades, a condition researchers call fetal microchimerism. The lingering of the fetal DNA, research suggests, may be a mixed blessing for a mom: The cells may benefit the mother's health—by promoting tissue repair and improving the immune system—but may also cause adverse effects, such as autoimmune reactions.
One question is how leftover fetal cells affect the brain. Researchers have shown that fetal microchimerism occurs in mouse brains, but they had not shown this in humans. So a team led by autoimmunity researcher and rheumatologist J. Lee Nelson of the Fred Hutchinson Cancer Research Center in Seattle, Washington, took samples from autopsied brains of 59 women who died between the ages of 32 and 101. By testing for a gene specific to the Y chromosome, they found evidence of male DNA in the brains of 63% of the women. (The researchers did not have the history of the women's pregnancies.) The male DNA was scattered across multiple brain regions, the team reports online today in PLoS ONE.
Because some studies have suggested that the risk of Alzheimer's disease (AD) increases with an increasing number of pregnancies, the team also examined the brains for signs of the disease, allowing them to determine whether AD correlated with the observed microchimerism. Of the 59 women, 33 had AD—but contrary to the team's expectation, the women with AD had significantly less male DNA in their brains than did the 26 women who did not have AD.
Whether that correlation means that fetal male DNA helps protect women against AD is unclear, however. "To me, this suggests that the presence of fetal cells in the female brain prevents disease," says cardiologist Hina Chaudhry of Mount Sinai School of Medicine in New York City.
In a study published online in Circulation Research late last year, Chaudhry and colleagues found that fetal cells in mice migrated to the mother's heart, differentiated into functioning cardiac cells, and accelerated repair to damaged heart tissue. So, Chaudhry says, a similar thing could be happening when fetal cells migrate to the brain. "I would bet these cells are getting into the maternal brain and are able to differentiate into neurons."
A 2010 study in Stem Cells and Development showed that fetal cells can migrate to the brain of a mother mouse and mature into neurons, Nelson says. But, she adds, it remains unclear if something similar is happening in humans—and it's also difficult to reach any firm conclusions about a potential link between microchimerism and AD. Part of the problem is that her team had little information about the pregnancy histories of the women in their study. "We have to say we really don't know," she says. "I hope that kind of work can be done in the future, but it's very difficult to do with human samples."