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2015

A Pregnancy Souvenir: Cells That Are Not Your Own
New York Times, September 10, 2015
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Recently, a team of pathologists at Leiden University Medical Center in the Netherlands carried out an experiment that might seem doomed to failure.

They collected tissue from 26 women who had died during or just after pregnancy. All of them had been carrying sons. The pathologists then stained the samples to check for Y chromosomes.

Essentially, the scientists were looking for male cells in female bodies. And their search was stunningly successful.

As reported last month in the journal Molecular Human Reproduction, the researchers found cells with Y-chromosomes in every tissue sample they examined. These male cells were certainly uncommon — at their most abundant, they only made up about 1 in every 1,000 cells. But male cells were present in every organ that the scientists studied: brains, hearts, kidneys and others.

In the 1990s, scientists found the first clues that cells from both sons and daughters can escape from the uterus and spread through a mother’s body. They called the phenomenon fetal microchimerism, after the chimera, a monster from Greek mythology that was part lion, goat and dragon.

But fetal cells don’t just drift passively. Studies of female mice show that fetal cells that end up in their hearts develop into cardiac tissue. “They’re becoming beating heart cells,” said Dr. J. Lee Nelson, an expert on microchimerism at the Fred Hutchinson Cancer Research Center in Seattle.

The new study suggests that women almost always acquire fetal cells each time they are pregnant. They have been detected as early as seven weeks into a pregnancy. In later years, the cells may disappear, but sometimes, the cells settle in for a lifetime. In a 2012 study, Dr. Nelson and her colleagues examined the brains of 59 deceased older women and found Y-chromosomes in 63 percent of them. (Many studies on fetal microchimerism focus on the cells left behind by sons, because they are easier to distinguish from the cells of their mother.)

Experts now believe that microchimerism is far from rare. “Most of us think that it’s very common, if not universal,” Dr. Nelson said. But it remains quite mysterious.

In recent years, researchers have found many clues suggesting that microchimerism can affect a woman’s health. Tumors may be loaded with fetal cells, for example, suggesting that they might help drive cancer. Yet other studies have suggested that fetal microchimerism protects women against the disease.

“In each instance of a disease, it seems like there is this paradox,” said Amy M. Boddy, a postdoctoral fellow at Arizona State University.

Fetal microchimerism has been found in a number of mammal species, including dogs, mice and cows. It’s likely that fetal cells have been a part of maternal life for tens of millions of years.

“Microchimerism is something that humans have been evolving with since before we were humans,” said Melissa Wilson Sayres, a biologist at Arizona State.

During that time, fetal cells could have evolved into more than just bystanders. Writing in the journal Bioessays last month, Dr. Boddy, Dr. Sayres and their colleagues suggested that fetal cells may produce chemicals that influence the mother’s biology, allowing ftuses to manipulate her from within.

Some cells may help maintain the health of the mother — for example, by healing wounds. But there is also an evolutionary conflict of interest between mothers and their young.

A mother’s reproductive success depends on the total number of children she raises to adulthood over the course of her life. Devoting too many resources to a single child may leave her too frail to care for later children.

If a child can somehow coax its mother to provide more resources, on the other hand, he or she may be more likely to survive to adulthood and reproduce. Fetal cells may let children manipulate their mothers to this end, Dr. Sayres and her colleagues propose.

Fetal cells are frequently found in breast tissue, even in milk, for instance. The researchers argue that children might thrive more if their fetal cells drove up milk production.

Mothers also nurture their babies with body heat. The thyroid gland, located in the neck, acts like a thermostat, and fetal cells in the thyroid gland in theory could cause mothers to generate more heat than they would otherwise.

This biological tension might help explain how fetal microchimerism sometimes causes harm to a mother. It may simply be an occasional side effect of the cells’ manipulations.

There are some clues that mothers, too, pull hard in this evolutionary tug of war. The immune system kicks into high gear after giving birth, possibly to clear away leftover fetal cells. This defense may pose its own risks: Women with autoimmune disorders such as rheumatoid arthritis can have relapses after pregnancy.

Some straightforward experiments could put all of these ideas to the test. Scientists could look at which genes become active in fetal cells in different parts of the body, for example. They could then see how the activity of the genes influenced a mother’s physiology, such as the production of milk.

If the preliminary results hold up, Dr. Boddy and her colleagues suggest that scientists also should consider how fetal cells in the brain might influence women’s behavior.

“It’s the most exciting part, but it’s the part where there’s the least research at the moment,” said Athena Aktipis, a psychologist at Arizona State and an author of the Bioessays article. “There may be a role of microchimerism in postpartum mental health.”

Dr. Nelson, who was not involved in the new paper, said that it raised a lot of ideas worth pursuing.

“It’s going to be interesting to see how the data coming in over the next several years stacks up,” she said.

Copyright 2015 The New York Times Company. Reproduced with permission.
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