THURSDAY, Sept. 21, 2023 (HealthDay News) -- One pregnancy may leave behind microscopic souvenirs that prepare a mom's immune system for the next one, a new study suggests.
Experts said the research, carried out in lab mice, offers new insights into a longstanding puzzle: Why doesn't a pregnant woman's immune system attack the fetus, which is essentially a foreign invader?
Scientists do not fully understand how that immune tolerance works. But the new findings suggest that once a woman has a healthy pregnancy, that fetus leaves behind tiny populations of cells that help maintain a hospitable environment for the next pregnancy.
The hope is that research like this will eventually lead to ways to prevent pregnancy complications -- including pre-eclampsia, preterm birth and stillbirth, according to senior researcher Dr. Sing Sing Way.
At their root, those complications all involve a level of "fetal intolerance," said Way, a professor at Cincinnati Children's Hospital Medical Center.
An expert not involved in the study agreed.
Understanding how the maternal immune system successfully accepts a fetus is "a way of getting at the causes of pregnancy complications," said Dr. Linda Randolph, head of medical genetics at Children's Hospital Los Angeles.
If future research confirms similar mechanisms in humans, she said, there could be important implications for preventing those complications, including pregnancy loss.
The findings — published Sept. 22 in the journal Science — are based on lab mice, because their pregnancies are obviously much easier to study. But there is already evidence, Way said, that the results could also hold true for human pregnancies.
Plus, he noted, while mice may be mice, all species have the same challenge when it comes to reproduction: How does the female body avoid rejecting the fetus?
The new research connects two intriguing phenomena. One is known as fetal microchimerism, where a small number of fetal cells escape the womb and take up residence in various tissues throughout the mother's body. Researchers have long known that this happens (and that maternal cells end up in offspring, too).
But it's not fully clear what those fetal cells do after they settle into mom's tissues.
The other phenomenon is one Way's team found in a 2012 study published in Nature. They discovered that after a healthy pregnancy, the mother's body maintains a long-term supply of protective T-cells -- ones that recognize the next fetus produced by the same couple and help suppress an immune system reaction. That cell supply, in fact, can be maintained for years after the first birth.
The question was how? In other scenarios, like immunity from infection, "memory" immune cells often need some kind of low-level exposure to the foreign invader for their upkeep.
The new findings offer an answer: Fetal microchimerism. Those pockets of fetal cells left behind from the first pregnancy help maintain the "friendly" immune environment for a future sibling who is from the same father, Way explained.
If that sounds like sibling love, Way said it could be seen as a bit of a "selfish" act -- namely, the natural drive to propagate one's own genes. (Siblings from the same two parents share about half of their genes.)
The story does not end there, though.
After a subsequent pregnancy, the new research shows, cells from that fetus completely displace those from the older sibling in mom's body. But a small pool of the beneficial T-cells from each pregnancy lives on, to be called into action for the next one.
According to Way, the findings align with patterns seen in human pregnancy complications: They are more common in a first pregnancy, but if that initial pregnancy is a healthy one, the likelihood of complications the next time is even lower.
In contrast, if a woman suffers a complication like pre-eclampsia, preterm birth or stillbirth, she has a higher-than-average risk of that complication in subsequent pregnancies.
Way said the new findings raise an important question: If a mom's immune system "remembers" a healthy pregnancy, does it also retain the memory of a complicated one?
If that can be unraveled, Way said, it could lead to ways to prevent recurrent pregnancy complications.
Randolph agreed that is the potential clinical implication down the road. From a broader standpoint, she said, the findings are a "remarkable testament" to the complexity of reproduction.
More information
The U.S. Centers for Disease Control and Prevention has more on pregnancy complications.
SOURCES: Sing Sing Way, MD, PhD, chairman, Division of Infectious Diseases, professor, pediatrics, Cincinnati Children's Hospital Medical Center, Ohio; Linda Randolph, MD, head, medical genetics, co-director, neurofibromatosis clinic, Children's Hospital Los Angeles; Science, Sept. 22, 2023
