Fetal Microchimerism

by Grace Chen

In Greek mythology, a chimera was a grotesque monster formed of a conglomeration of different animal parts….

With the head of a goat, body of a lion, and tail of a snake, the chimera was a fearsome but reassuringly fictional concept. Today, however, scientists know that real-life chimeras do indeed exist. The term has become used to describe a number of biological phenomena that produce organisms with cells from multiple different individuals.1 Far from being monsters, artificial chimeras include many of the GMO crops that are feeding the world’s growing population, as well as genetically engineered bacteria that produce insulin and other key drugs in marketable quantities.2 Research in human developmental biology is now showing, however, that we ourselves may be naturally occurring chimeras.

The phenomena of fetal microchimerism describes the presence of living cells from a different individual in the body of placental mammals . The placenta generally serves as a bridge between the fetus and the mother for exchange of nutrients and wastes. But that is not all that crosses this bridge—fetal and maternal cells can cross between the two organisms intact. While maternal cells do end up in the fetus, significantly more fetal cells are transferred to the mother.3 The result is that the mother carries a small number  of foreign cells belonging to her fetus within her body—hence the name “microchimerism.” While these non-maternal cells are few in number in comparison to total number of maternal cells, evidence suggests that these transplanted cells can actually remain for long after the end of gestation. In fact, derivative fetal cells have been found in the mother’s body up to 27 years after pregnancy.4

From an evolutionary standpoint, selective pressures favor traits that increase reproductive fitness of the individual; because the mother and fetus share so much genetic material, these invasive cells ought to share the same interests as the mother’s cells in promoting mutual welfare. Yet, pregnancy in placental mammals can also be seen as a tug-of-war between fetal and maternal interests, as finite biological resources must be allocated between the two organisms. Effects caused by these microchimeric cells that favor the fetus’ well-being, however, might be detrimental to the mother’s welfare, or to the welfare of future offspring.5 This creates an interesting paradox for evolutionary biologists: what is the nature of the interaction between these cells that ought to be cooperative but also conflicting?

Answering such questions will require further research on this poorly understood phenomenon. One easy way that scientists have been able to detect and quantify the presence of non-maternal cells in the mother’s body is by searching for the presence of Y chromosomes, found only in male cells, in the mother’s body. Presumably, any Y chromosomes would indicate the presence of intact cells from a prior male fetus, as female sex chromosomes are exclusively X chromosomes.6 Though feto-maternal microchimerism is the most common source of these invader cells, several hypotheses have also been proposed to explain why Y chromosome microchimerism has also been found in about a fifth of women who have not had a male fetus. Some of these alternative explanations include spontaneously aborted male zygotes, or chimeric cells from an older male sibling acquired in utero from their own mother.7

A common technique implemented in hunting down the location of foreign cells is called fluorescent in situ hybridization (FISH), wellknown to most genetics students. After a tissue sample is isolated and prepared, nucleic acid probes specific to genes on the Y chromosome are added.8 These probes are attached to a fluorescent dye, hence providing a visual cue of where they bind and thus where the Y chromosomes are found.9 Increasingly refined techniques are now allowing more specific searches; for instance, fluorescent probes can be used to identify microchimeric cells with specific allele differences from maternal cells.

WHERE DO THESE TINY INVADERS GO?

Invading fetal cells are commonly found in the bloodstream, but can travel much further than that. Fetal microchimerism has been recorded in the liver, bone marrow, thyroid, heart, and more. A recent study by the Fred Hutchinson Cancer Research Center found that more than 60 percent of autopsied brains contained copies of DNA from another individual.10 There is also interesting evidence that these undifferentiated fetal cells can serve as stem cells within the mother’s body—a study in mice suggested that fetal cells can develop into mature neurons within the mother’s brain.11 These invader cells, it seems, can make themselves fully at home in the host body. The locations that the fetal cells tend to settle down in may yet reveal more about the evolutionary pressures affecting this phenomena.

Thus the presence of microchimeric fetal cells in the mother’s body is now known to be widespread and long-lasting, but their effects remain ambiguous. Conflicting studies have linked the presence of fetal cells to both improved and worsened health outcomes for the mother for different diseases in different scenarios. A richer understanding the effects on maternal health, as outlined below, can shed light on not only key issues of women’s health, but also more broadly on the response of the immune system to invaders.

Grace Chen ‘19 is a freshman in Holworthy Hall.

Works Cited

  1. Bowen, R.A. Mosaicism and Chimerism. Colorado State University Hypertextsfor Biomedical Sciences: General and Medical Genetics [Online], August 5, 1988, p2. http://arbl.cvmbs.colostate.edu/hbooks/genetics/medgen/chromo/mosaics.html (accessed Oct. 1, 2015).
  2. Simpson, T. GMO: Part 2 – The Promise, the Fear, Labeling, Frankenfoods. Your Doctor’s Orders [Online], May 15, 2013, p 1-3. http://www.yourdoctorsorders.com/2013/05/gmo-part-2the-promise-fear-frankenfoods/ (accessed Oct. 1, 2015).
  3. Boddy, A. M. et al. Bioessays 2015, 37, 1106–1118.
  4. Bianchi D.W. et al. Proc Natl Acad Sci U S A  1996, 93, 705–708.
  5. Adams, K. M. et al. Journal of American Med. Assn. 2004, 291, 1127-1131.
  6. Kean, S. You and Me. Psychology Today [Online], March 11, 2013, p 1-4. https://www.psychologytoday.com/articles/201303/the-you-in-me (accessed Oct. 1, 2015).
  7. O’Connor, C. Nature Education. 2008, 1, 171.
  8. Chan, W.F.N. et al. PLoS ONE. 2012, 7.
  9. Zeng, X.X. et al. Stem Cells and Development. 2010, 19, 18191830.
  10. Centers for Disease Control and Prevention. http:// http://www.cdc.gov/parasites/naegleria/ (accessed Oct. 4, 2015).

 

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