First Evidence of Foetal DNA Persisting in Female Human Brain Tissue

Long-lasting foetal microchimerism in maternal brain is common, affects many brain regions

Thursday, 27 September 2012

Small portions of male DNA, most likely left over in a mother's body by a male foetus can be detected in the maternal brain relatively frequently, according to a report published Sep. 26 in the open access journal PLOS ONE by William Chan of Fred Hutchinson Cancer Research Center and his colleagues.

This shows a male cell in female human brain.

Credit: Citation: Chan WFN, Gurnot C, 

Montine TJ, Sonnen JA, Guthrie KA, et al. 

(2012) Male Microchimerism in the Human 

Female Brain. PLoS ONE 7(9): e45592, 

doi:10.1371/journal.pone.0045592.

The process, called foetal 'microchimerism (Mc)’, is common in other tissues such as blood, but this is the first evidence of male Mc in the human female brain. Microchimerism can be both beneficial and harmful to maternal health, since it is associated with processes such as tissue repair, as well as to autoimmune diseases.

Testing for the presence of a particular region of the Y-chromosome in autopsied brain tissues, the research team discovered that 63% of their samples showed potentially long-lasting Mc in multiple brain regions. They also found that women with Alzheimer's disease (AD) had less Mc than women without the disease.

According to the authors, this result warrants further investigation because previous reports have suggested that AD may be more prevalent in women with a higher number of pregnancies compared to childless women. The researchers commented that changes to the blood-brain barrier that occur during pregnancy could facilitate the process by which Mc is acquired into the human brain.

"This is the first evidence that microchimerism can cross the blood-brain barrier to establish male foetal tissue in the human female brain" says Chan.

Source: Public Library of Science 

Contact: Jyoti Madhusoodanan

Reference:

Male Microchimerism in the Human Female Brain 

Chan WFN, Gurnot C, Montine TJ, Sonnen JA, Guthrie KA, Nelson JL

PLoS ONE 7(9): e45592 (2012), doi:10.1371/journal.pone.0045592

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Microchimerism: Foetal Cells Can Migrate Into Maternal Organs During Pregnancy

Some mothers literally carry pieces of their children in their bodies

Saturday, 09 June 2012

A pregnant woman's blood stream contains not only her own cells, but a small number of her child's, as well, and some of them remain in her internal organs long after the baby is born. Understanding the origin and identity of these cells is vital to understanding their potential effects on a mother's long-term health. For example, foetal cells have been found at tumour sites in mothers, but it is unknown whether the cells are helping to destroy the tumour or to speed its growth.

Three types of foetal cells have now been identified in the lungs of late-term pregnant mice by a team led by Dr. Diana Bianchi of Tufts Medical Center. The research, published 6 June 2012 in Biology of Reproduction's Papers-in-Press, used publicly available databases to extract important genetic information from as few as 80 foetal cells. A combination of two different analytical techniques to characterize the rare foetal cells revealed a mixed population of trophoblasts (placental cells that provide nutrients to the foetus), mesenchymal stem cells (cells that later develop into fat, cartilage, or bone cells), and immune system cells.

Researchers suspect that foetal cells in a mother's blood stream help her immune system tolerate and not attack the foetus. The detection of trophoblasts and immune cells in the maternal lung should aid future studies on this subject, as well as research into pregnancy-related complications like preeclampsia. The presence of foetal mesenchymal stem cells corresponds with previous studies that reported foetal and placental cells differentiating to repair injured maternal organs in both mice and humans.

Using this team's techniques of gene expression analysis, researchers should now be better able to identify the types of cells present in maternal organs and in doing so determine their potential short- and long-term effects on a mother's internal systems.

Source: Society for the Study of Reproduction 

Contact: Jeremy Lechan

Reference:

Comprehensive analysis of genes expressed by rare microchimeric fetal cells in maternal lung

Pritchard S, Wick HC, Slonim DK, Johnson KL, Bianchi DW.

Biol Reprod 2012; Published online ahead of print 6 June 2012; DOI 10.1095/biolreprod.112.101147

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Microchimerism: The Ties That Binds

Mothers and offspring can share cells throughout life — with positive and negative effects 
Friday, 02 May 2008 


Cutting the umbilical cord doesn't necessarily sever the physical link between mother and child. Many cells pass back and forth between the mother and foetus during pregnancy and can be detected in the tissues and organs of both even decades later. This mixing of cells from two genetically distinct individuals is called microchimerism. The phenomenon is the focus of an increasing number of scientists who wonder what role these cells play in the body. A potentially significant one, it turns out. Research implicates that maternal and foetal microchimerism plays both adverse and beneficial roles in some autoimmune diseases as well as the prevention of at least one cancer. This double-edged sword in turn has opened new avenues of study of the body's immune system and the possibility of developing new tests and therapies. 


 Two of the world's leading researchers in microchimerism are J. Lee Nelson, M.D., of Fred Hutchinson Cancer Research Center's Clinical Research Division; and V.K. Gadi, M.D., Ph.D., assistant professor of medicine at the University of Washington. Nelson also is a professor of medicine at the University of Washington. Gadi is also a research associate in the Hutchinson Center's Clinical Research Division. In 2007, they were the first to report these potentially beneficial effects of microchimerism:

• In January, Nelson reported the first discovery that cells passed from mother to child during pregnancy can differentiate into functioning islet beta cells that produce insulin in the child. The same study also found maternal DNA in greater amounts in the blood of children and young adults with Type 1 diabetes than their healthy siblings and a control group, implying that the cells may be attempting to repair damaged tissue. There was no evidence that the mother's cells were attacking the child's insulin cells and no evidence that the maternal cells were targets of an immune response from the child's immune system. The findings could lead to new approaches to treating Type 1 diabetes. For example, if maternal microchimerism results in cells that make insulin, a mother's stem cells might be harvested and used to treat her diabetic child. Such cells would have a genetic edge over donated islet cells from a cadaver that are usually completely genetically mismatched.

• Last October, a research paper by Gadi and Nelson described findings that suggest foetal cells that persist in a woman's body long after pregnancy in some cases may reduce the woman's risk of breast cancer. The scientists examined the blood of 82 women post-pregnancy, 35 of whom had had breast cancer. They looked for male DNA in the blood, presuming it was present due to a prior pregnancy with a male. Foetal microchimerism (FMc) was found significantly more often in healthy women than women with a history of breast cancer, 43 percent versus 14 percent respectively. The scientists concluded that FMc may contribute to the reduction of breast cancer based on the hypothesis that residual foetal cells may provide immune surveillance of malignant cells in the mother. They caution that further studies are needed to confirm the theory.

Microchimerism reveals its Jekyll and Hyde personality in the case of autoimmune diseases. In the late 1990s, Nelson's group was the first to investigate microchimerism in an autoimmune disease:

• In 1996 Nelson's lab proposed that foetal microchimerism might in part explain the female predilection to autoimmune disease and they subsequently discovered elevated levels of foetal microchimerism in the blood of women with scleroderma compared to healthy women. Subsequent studies found foetal microchimerism in internal organs and in skin affected by scleroderma.

• In 1999 Nelson's group found that maternal microchimerism persists into adult life in individuals who have normal immune systems. They presumed this is due to engraftment with maternal stem cells. Stem cells can become multiple different types of cells. Researchers wondered whether maternal cells can become part of the cells that make up tissues. Scientists found maternal cells in the hearts of infants who died from heart block due to neonatal lupus and identified that most of the maternal cells were cardiac myocytes (heart muscle cells). They theorized that the maternal cells are the target of an immune attack.

• On the other hand, women with rheumatoid arthritis often have their disease improve or even disappear during pregnancy. A beneficial role of foetal microchimerism was suggested by the research finding that elevated levels of foetal microchimerism significantly correlated with pregnancy-induced amelioration of rheumatoid arthritis.

The Nelson lab has expanded its study of microchimerism into the fields of reproduction, HIV/AIDS and transplantation. For example, scientists are investigating microchimerism in complications of pregnancy, especially preeclampsia, a disorder characterized by high blood pressure in women in their third trimester of pregnancy, and in recurrent pregnancy loss. Nelson's group also is investigating maternal microchimerism in patients with HIV and is looking at whether maternal microchimerism levels correlate with whether there is progression or non-progression to AIDS. Transplantation of stem cells to treat some cancers results in chimerism. Graft-vs.-host disease occurs more often if the cell donor is a woman with prior pregnancies. 


Tests of female donor cells found they contained male microchimerism, consistent with the interpretation that foetal microchimerism contributes to graft-vs.-host disease. In kidney, pancreas and islet transplantation, Gadi, Nelson and collaborators tested serial serum samples and found that donor-specific microchimerism detection may become a useful non-invasive test for early rejection. This has led to work by several other research groups to therapeutically exploit the principles of naturally-acquired microchimerism in their selection of donors for transplantation. 


The discovery that a mother's cells can turn up in her adult progeny and that foetal cells can occur in women who were once pregnant heralds the emergence of microchimerism as an important new theme in biology.


About Fred Hutchinson Cancer Research Center At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. 
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