Subvert your cognition! The most mysterious cells in our body do not belong to us?

© Ranta Images/Getty; Burazin

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Dr. J. Lee Nelson in the article conducted an experiment in 2012. She and her team collected autopsy samples from the brains of 59 deceased women. Testing the genes specific to the Y chromosome found that 63% of these women had male DNA in their brains, and the male DNA was distributed in different parts of the brain (the researchers did not have their pregnancy data).

Because some studies have shown that more pregnancies increase the risk of Alzheimer's disease, the research team also tested the brain to find signs of Alzheimer's disease to determine whether Alzheimer's disease is related to maternal-fetal microchimerism. Of the 59 women, 33 developed Alzheimer's disease - but the results were very different from what the research team expected. The women with Alzheimer's disease had significantly less male DNA in their brains than the 26 women without the disease.

(journals.plos.org/plosone/article?id=10.1371/journal.pone.0045592)

However, it remains unclear whether male fetal DNA reduces the risk of Alzheimer's disease in women.

About 24 years ago, Diana Bianchi peered through a microscope at a piece of human thyroid tissue and what she saw gave her goose bumps. The sample came from a woman with XX chromosomes. But through the lens, Bianchi saw distinct Y chromosomes, dozens or more. “Clearly,” Bianchi told me, “a portion of her thyroid gland was made entirely of male material.”[1]

Bianchi suspected that the reason might be pregnancy.

Years earlier, the patient had been pregnant with a male embryo, whose cells at some point wandered outside the uterus. They ended up in the mother’s thyroid gland and almost certainly in a few other organs, taking on the identities and functions of the female cells around them so they could work in tandem. Bianchi, now director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, was astounded: “Her thyroid gland had been completely transformed by her son’s cells.”

This woman's case is not isolated.

Almost every time an embryo implants and begins to grow, it sends parts of itself into the host that bred it. This begins at least as early as four or five weeks of gestation.[2] They are integrated into nearly every part of our anatomy that scientists have examined—heart, lungs, breasts, colon, kidneys, liver, brain, etc. The cells may stay there, growing and dividing for decades, or even, as many scientists suspect, for life, integrated into the host that bred them.[3]

They can almost be thought of as evolution’s original organ transplants, J. Lee Nelson of the Fred Hutchinson Cancer Center told me. Microchimerism is probably the most common way that genetically identical cells mature and develop simultaneously in two bodies.

© Wikipedia

These intergenerational transfers go both ways. As fetal cells cross the placenta and enter maternal tissues, a small number of maternal cells also migrate into fetal tissues and may persist into adulthood. Thus, gene exchange may occur several times during a lifetime. Some researchers have suggested that people may be miniature copies of many relatives, passed down through chains of pregnancy[4]: perhaps their brothers and sisters, their grandmother[5], or any aunts or uncles that their grandmother was pregnant with before their mother was born.

“It’s like your entire family is inside you,” Francisco Úbeda de Torres, an evolutionary biologist at the Royal Holloway University in London, told me.

© ThoughtCo

All of which makes microchimerism (named after the Greek mythological creature Chimera, which had the torso of a lion, the middle of a goat and the lower body of a dragon) more common than pregnancy itself, and is believed to affect everyone who has ever carried a fetus, even briefly, and every life that has ever existed in the womb.

Other mammals, such as mice, cows, and dogs, as well as our closest primate relatives, seem to carry this cellular heritage. But the borrowed cells don’t always appear in the same numbers and in the same places. In many cases, microchimeric cells are thought to exist at concentrations of about one per million cells—“close to or at the limit of detection for many biological assays,” Sing Sing Way, an immunologist and pediatrician at Cincinnati Children’s Hospital, told me.

Some scientists have argued that such sparse and inconsistent cells could not possibly have a meaningful effect. Even within the field of microchimerism, the hypothesis that these cells play any role remains “highly controversial,” Wei said.

But many experts believe that microchimeric cells are not just passive passengers drifting in a sea of ​​someone else’s genes. They are unique genetic entities in a foreign environment, with their own evolutionary motivations that may come into conflict with their hosts. They could influence many aspects of health: our susceptibility to infectious diseases or autoimmune diseases, the success of pregnancies, and perhaps even everyday behavior.[6] If these cells prove to be as important as some scientists believe, they may be among the most underappreciated architects of human life.

Researchers have already found clues to the purpose of these wandering cells. Wei’s studies on mice, for example, suggest that microchimerism inherited by babies during pregnancy may help fine-tune their immune systems, enabling newborns’ bodies to fight off viral infections. As the rodents age, their mothers’ cells may see fetuses made of half-foreign DNA as benign rather than as unfamiliar threats, helping them carry pregnancies to term.

© Transplantation and Cellular Therapy

Similarly, some studies have found that genetic microchimerism may help explain why people are more likely to accept organs from their mothers than from their fathers, says William Burlingham, a transplant specialist at the University of Wisconsin at Madison. In the early 1990s, Burlingham treated a kidney transplant patient who suddenly stopped taking his immunosuppressant drugs, a move that should have prompted his body to reject the new organ. But “he was doing fine,” Burlingham told me. The patient’s kidney had come from his mother, whose cells were still circulating in his blood and skin; when his body encountered the transplanted tissue, it recognized the new member as its own.

Even fetal cells that drift into the mother’s body during pregnancy may promote the baby’s health. David Haig, an evolutionary biologist at Harvard University, has suggested that these cells may position themselves to optimally extract resources from the mother[10] : in the brain, to gain more attention; in the breast, to stimulate more milk secretion; in the thyroid gland, to induce more body heat.

David Haigh told me that these cells might also regulate the mother’s fertility, spacing births longer and providing more continuous care for the infants. Ubeda de Torres said that fetal cells could serve as informants for future offspring that inhabit the same uterus. If future fetuses do not feel a sense of kinship with their older siblings, they might become more greedy in taking nutrients from their mothers, leaving less for future siblings to whom they might not be as closely related.[11]

For mothers, the benefits of microchimerism are harder to pin down.[12] One possibility is that the more thoroughly the embryonic cells infiltrate the mother, the better she will be able to tolerate the fetal tissue, thereby reducing the chances of miscarriage or high-risk childbirth. “I really think of this as an insurance policy for the mother,” Amy Boddy, a biological anthropologist at the University of California, Santa Barbara, told me. “It’s like, ‘Hey, don’t attack me.’ ” After childbirth, the cells that remain in the mother’s body might also play a role in future pregnancies (at least if the father is the same).

The more pregnancies a woman has with the same partner, the rarer pregnancy complications such as preeclampsia become. And when mothers send cells to their babies, they may be able to give themselves a break by increasing their infants’ sleepiness or suppressing their fussiness.

© The Lancet

Microchimerism may not always be beneficial to the mother.

Nelson and other researchers have found[13] that women with more fetal cells are more likely to develop certain types of autoimmune diseases in the long term, perhaps because their daughters’ cells are mistakenly reassessed by some parts of the postpartum body as unwelcome invaders[14].

Working with mice, Nathalie Lambert, a postdoctoral fellow at Nelson's who is now at the French National Institute of Health and Medical Research, found that fetal microchimeric cells could also produce antibodies that spurred an attack on maternal cells.

But the picture may be more complicated than that. “I don’t think they’re bad actors,” Nelson said of the interloping fetal cells. She and her colleagues have also found that fetal cells can sometimes play a protective role against autoimmunity, leading to diseases such as rheumatoid arthritis that actually lessen during and shortly after pregnancy.

In other contexts, fetal cells may be both helpful and harmful to the mother, or not helpful at all. Microchimeric cells of fetal origin have been found to enter the heart tissue of mice that had experienced a mid-pregnancy heart attack, to colonize the pancreas of newly diabetic mouse mothers, and to lurk in human tumors and Caesarean section scars. But scientists are unsure whether these foreign cells are causing damage, repairing damage, or are simply bystanders found by chance in these locations.[15]

© Osteopathic Health Centre

Professor Wei told me that these questions are difficult to answer because microchimeric cells are notoriously difficult to study. They may exist in all of us, but they are still rare and often hidden in hard-to-access internal tissues. Researchers are not yet sure whether these cells are actively deployed to predetermined locations, pulled into specific organs by maternal cells, or simply flow naturally through the bloodstream like riverbed sediments.[16]

There is no consensus on how much microchimerism the body can tolerate. In the absence of evidence, even microchimerism researchers are bracing for possible disappointment. “My internalized view is that the vast majority of microchimerism is completely benign,” Melissa Wilson, a computational evolutionary biologist at Arizona State University, told me.

But if microchimeric cells do play a role in autoimmunity or reproductive success, the potential for treatment could be enormous. Burlingham told me that one option might be to infuse organ-transplant patients with cells from their mothers, which could act like tiny messengers to coax the body into accepting any new tissue. Boddy told me that microchimerism-inspired therapies could help alleviate the burden of high-risk pregnancies, many of which appear to be driven by inappropriately aggressive maternal immune responses.

© Joseph Daniel Fiedler/NPR

They could also improve the experience of surrogate mothers, who are more likely to experience pregnancy complications such as high blood pressure, premature birth, and gestational diabetes. The stem cell properties of these cells could even help researchers design better treatments for genetic diseases in utero. A team at the University of California, San Francisco, is applying this idea to treat thalassemia.[17]

Before these ideas can be put into practice, there are still some questions to be answered. Researchers have found that microchimeric cells from different sources can sometimes compete with one another, or even replace one another, for dominance. If that happens with future therapies, doctors may have to choose carefully which cells to introduce into a person’s body and when. And, perhaps most fundamentally, scientists are not yet sure how many microchimeric cells are needed to have an impact on a particular person’s health, a threshold that could determine how useful these theoretical therapies are, biological anthropologist Kristine Chua told me.

Even amid these uncertainties, experts insist on the importance of microchimerism: “These cells are so persistent, so common, so ancient, they must have an impact,” Boddy told me. “The simple fact that they are allowed to persist in the body for decades while growing, developing, and changing may teach us a lot about the immune system and ourselves.”

“It really changed my concept of myself, in my opinion,” Bianchi, who has a son now grown, told me. Even though the son is now grown, they haven’t really left each other.

References:

[1]www.thelancet.com/journals/lancet/article/PIIS0140-6736(01)07099-4/fulltext

[2]journals.sagepub.com/doi/10.1177/1753495X19884484

[3]www.ncbi.nlm.nih.gov/pmc/articles/PMC40117/

[4]pubmed.ncbi.nlm.nih.gov/35700729/

[5]www.thelancet.com/journals/ebiom/article/PIIS2352-3964(21)00515-6/fulltext

[6]www.nature.com/articles/s41467-022-32230-2

[7]www.nature.com/articles/nri.2017.38

[8]www.cell.com/cell/fulltext/S0092-8674(15)00843-0

[9]www.nejm.org/doi/full/10.1056/nejm199812033392302

[10]www.tandfonline.com/doi/full/10.4161/chim.29122

[11]royalsocietypublishing.org/doi/10.1098/rspb.2023.1142

[12]pubmed.ncbi.nlm.nih.gov/12848954/

[13]journals.sagepub.com/doi/10.1177/1753495X19884484

[14]pubmed.ncbi.nlm.nih.gov/26316378/

[15]pubmed.ncbi.nlm.nih.gov/22397765/

[16]pubmed.ncbi.nlm.nih.gov/33417673/

[17]www.sciencedirect.com/science/article/pii/S000649711870904X

[18]www.science.org/doi/10.1126/science.adf9325

By Katherine J. Wu

Translation/Yuba and Thin Bamboo

Proofreading/tim

Original article/www.theatlantic.com/science/archive/2024/01/fetal-maternal-cells-microchimerism/676996/

This article is based on the Creative Commons License (BY-NC) and is published by Yuzhu and Shouzhu on Leviathan

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