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Pregnancy changes the human body dramatically. One of the smallest alterations that pregnancy produces may also be the most important, suggests new research exploring cell populations passed between mother and child.
“During pregnancy, there’s a bi-directional transfer of cells, mother to baby and baby to mother,” says Dr. Sing Sing Way, the Pauline and Lawson Reed Chair for the Division of Infectious Diseases at Cincinnati Children’s Hospital Medical Center and a professor of pediatrics at the University of Cinncinnati. This is not surprising, given the essential connection formed between mother and child through the placenta. What is more of a shock is that these cells don’t disappear after birth. “One out of a million cells in our body is not our own,” explains Way in an interview with Technology Networks. His team’s research focuses on these “microchimeric” cells. Way is the senior author on a new paper, published in Science, that reveals how groups of these cells interact in the body.
Rare but important cells
Many scientists, let alone the general public, are unlikely to have heard of these microchimeric cells, says Way. They are vanishingly rare and are almost non-existent in our bloodstream. Instead, researchers have to look at individual tissues to track them down. Given the challenges posed by studying microchimeras, scientific thought wrote them off as an “accidental souvenir of pregnancy”, says Way. “A belly button is a remnant of in utero life. I think everybody would have a belly button if we examined them. But once you’re born, it actually serves no purpose. People thought that this microchimerism could also be a remnant from that perspective.”
But in 2015, Way and his team made a breakthrough in their ability to study these microchimeras, developing tools that let them track and experimentally reduce the numbers of microchimeric cells in mice. This study threw up two linked findings – an unusually high number of microchimeric cells made their home in female reproductive organs, and that these sparse cells might play an important role in cross-generational tolerance. The microchimeric cells that pass from mother to child, called maternal microchimeric cells, have immune signatures. When male and female mice reproduced, says Way, if the male mouse’s immune signature matched that of their partner’s microchimeric cells, pregnancy complications like spontaneous abortion or stillbirth were greatly reduced, suggesting that matching microchimeras act to provide immune protection to a growing fetus.
How many people’s cells are in here?
This study’s explanation of microchimeric cells’ purpose only raised more questions for Way’s team. In their latest work, the team explored how different populations of microchimeric cells interact. A mother of two children from two pregnancies will have had three sets of microchimeric cells in her body over the course of her life:
- Maternal microchimeric cells from her own mother
- Fetal microchimeric cells from her first child
- Fetal microchimeric cells from her second child
Would these different cell types play nicely with each other?
When female mice became pregnant, Way’s team looked to see what happened to the maternal microchimeric cells in their bodies. To the team’s surprise, the cells had entirely disappeared, replaced by new fetal microchimeric cells from the mouse’s pup. “It’s quite remarkable how efficient [the replacement] is,” says Way.
The same replacement was noted between pregnancies. In a mother’s body, the younger pup’s microchimeric cells displace those of their sibling. Way’s research does suggest that mother mice don’t entirely forget their offspring. Instead, a tiny fraction of immune cells that play a role in suppressing the wider immune response appear to remain in the body, allowing the mother to recall “memories” of their earlier pup.
A chain of immune tolerance?
The team isn’t sure how the replacement occurs between cell populations. It appears to be a deliberate and controlled “decision” by one set of cells to leave. “We don’t see evidence of rejection,” says Way. It also doesn’t look like the two sets of cells fight each other. Way’s team speculates in their paper that a set of cells passed from mother to daughter might evacuate the body when that daughter becomes pregnant, to migrate into the daughter’s growing fetus. This points at a chain of immune tolerance that has been flowing between generations, unnoticed by biologists.
Way’s next step is to investigate the flip side of their current work. “If mothers remember good pregnancies, do they also remember bad pregnancies?” says Way. He points out that human data suggests that if a mother experiences pre-eclampsia, which causes potentially severe high blood pressure during pregnancy, the risk of the same condition in future pregnancies is dramatically increased. What if microchimeric cells are to blame?
Microchimeric cells still remain mostly mysterious, but this work suggests that these tiny cell populations may have an outsized impact on human health.
Reference: Shao T, Kinder JM, Harper G, et al. Reproductive outcomes after pregnancy-induced displacement of preexisting microchimeric cells. Science. 2023;381(6664):1324–1330. doi:10.1126/science.adf9325