How Male DNA Gets in a Woman’s Brain

WOMEN DNA
Illustration by Oliver Munday for Newsweek

In case any doubt remained that guys get into girls’ heads, for the first time scientists have found male DNA in the human female brain. Researchers at the Fred Hutchinson Cancer Research Center in Seattle examined dozens of women’s brains and discovered that the majority of them contained genetic material found only on the Y chromosome.

This material almost certainly isn’t found in girls’ genomes when they’re born (except in cases of rare genetic abnormalities). So when material from the Y chromosome is found in women’s bodies, a phenomenon more broadly called microchimerism, scientists suspect that it somehow got in later on. But how?

The most likely explanation is that during a pregnancy cells from a male fetus slipped across the placenta, circulated in the mother’s body and lodged in her brain. In the new work, made public in September in the journal PLOS ONE, J. Lee Nelson, an immunogeneticist, and her colleagues examined autopsy specimens from 59 women and found that 63 percent of them had male genetic material in their brains. (Cells from a female fetus can also slip in, but they are harder to detect in the mother, hence the focus on sons.) Even for those who’ve never given birth to sons, a pregnancy that ended in abortion or miscarriage can also lead to microchimerism. (So can blood transfusions of nonirradiated blood, as trauma victims sometimes receive, and so can having a twin, including one that disappeared in utero.)

While microchimerism has been found in other parts of the body, the discovery extends the phenomenon to the human brain. And it energizes many questions about how this curious mix of self and other functions in our bodies—and how its presence in such a crucial and sensitive organ might differ. To start with, researchers are not sure how, exactly, fetal cells or genetic material is tolerated by the mother’s immune system, which can go into attack mode when foreign or semiforeign material enters the body. Researchers also wonder how the new cells manage to stick around for so long and in what form: the oldest subject in the autopsy study was 94, meaning that male DNA that arrived during pregnancy could have been there for more than half a century.

Most importantly, they puzzle over whether this semiforeign material is detrimental or beneficial to the host mother. “The question,” explains Diana Bianchi, a reproductive geneticist and professor at Tufts University School of Medicine, “is whether it is helping or hurting.” And as the burgeoning literature on autoimmune diseases, cancer, and tissue injury and repair suggests, the answer is probably some of both.

On the negative side of the ledger, studies now suggest links to autoimmune diseases, like scleroderma, lupus, and in some cases rheumatoid arthritis, a disorder in which the joints become inflamed, causing pain and decreased mobility. Rheumatoid arthritis (like scleroderma and lupus) is known to affect more women than men. It also has a strong genetic basis. But there are -women who suffer from this form of arthritis who do not have the most common genetic risk factors. As French researcher Nathalie Lambert found, these women were more likely to have a particular type of microchimerism—a type that itself was more likely to include a genetic variant associated with the disease. It’s possible, then, that many of these women acquired genetic risk factors from their fetuses. If that’s the case, “it’s almost a reverse inheritance, isn’t it?” says Nelson. Her lab conducted a similar study in 2011 and reached the same conclusion. (Neither paper proves that microchimerism caused the women to develop rheumatoid arthritis, though both show a compelling association.) A similarly adverse finding exists for colon cancer: in one study, those with higher levels of microchimerism seemed to be more likely to develop cancer later on.

On the other hand, higher levels of microchimerism may protect some women from breast cancer. Analyzing blood samples taken from a group of Danish women in the 1990s, V.K. Gadi, an oncologist at the University of Washington, and his colleagues recently found that the women who had less microchimerism back then were more likely to have developed breast cancer a decade later. In other words, not having this foreign genetic material, perhaps from a fetus, seemed to increase their chances of getting the disease, says Gadi. “It’s as if they were missing something that might have been protective.”

What are fetal cells doing, precisely, in the mother’s body? Studies in animals and people have shown that some of them can mature, or differentiate, into various kinds of adult cells. They also tend to appear in higher concentrations at sites of injury, which could mean that they’re contributing to the injury—or helping to repair it. From an evolutionary perspective, says Bianchi, “the -fetus has a vested interest in keeping its mother alive,” not only while it’s in utero but for many years to come. It could be that “the fetus is giving these cells to its mother to promote her healing.”

Strange as that may sound, cardiologist Hina Chaudhry at Mount Sinai School of Medicine in New York recently found evidence for this view in a study of heart attacks. Working with pregnant mice that had been genetically engineered, she and her colleagues were able to track the movement of fetal cells within the mother’s body. When the researchers caused the mothers to have heart attacks, they observed that fetal cells homed in on the injured tissue. Indeed, the cells embedded themselves in the maternal heart and differentiated into new heart muscle cells, capable of beating. It’s an elegant finding, suggesting that the “baby gives back,” says Bianchi.

Fetal cells are a diverse group. And what they do in the mom’s body may depend on how mature they are, what gene variants they’re carrying, and what types of cells are involved, says Nelson. “This is not just one kind of cell doing one thing.” But given their irrefutable presence in major organs—now including the brain—“we can’t afford to ignore them,” Bianchi adds. “We need to pay a lot more attention to what they’re doing.”

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