Debunking myths on genetics and DNA

Friday, March 21, 2014

I carry my son's DNA: a look at microchimerism and its effects

To celebrate the upcoming release of my detective thriller CHIMERAS, the next few Research Blogging posts will be dedicated to the different forms of chimerism. I'm sure you are all familiar with dispermic chimeras, which occur when two fertilized eggs fuse together shortly after conception. The result is one individual with two sets of genetically distinct cells.

Have you ever heard of microchimerism, though?
"Microchimerism refers to a small number of cells (or DNA) harbored by one individual that originated in a genetically different individual. While microchimerism can be the result of interventions such as transplantation or transfusion, by far the most common source is naturally acquired microchimerism from maternal-fetal trafficking during pregnancy [1]."
Before the 1960s, it was believed that the placenta was a perfect barrier between mother and fetus, and no blood or cells could trespass it in either direction. Today we know that there's actually a two-way exchange of cells between mother and fetus during pregnancy. What's even more surprising is that these "extraneous" cells outlast the duration of the pregnancy and can in fact be found in the child and/or the mother years after birth. Male DNA has been found in women years after they had given birth to their sons. In fact, fetal cells are released in high quantities during spontaneous abortions, hence can be found even in women who have never delivered, so long as at some point in their lives they became pregnant.

This of course prompts the following question: is microchimerism beneficial to the mother's and/or child's health?

The answer is yes and no.

For example, things can go wrong when the mother develops some kind of malignancy during pregnancy: there have been cases in which metastases from a maternal melanoma were acquired by the baby through transplacental transfer. Conversely, it has been noted that the amount of fetal DNA circulating in the mother is higher in cases where there are anomalies in the fetus's chromosome count and in pregnancies complicated by eclampsia (seizures).

Where is the fetal DNA found? Just about everywhere: liver, thyroid, cervix, gallbladder, intestine, spleen, lymph nodes, heart, and kidneys. Once they enter the maternal system, the fetal cells act effectively as an engrafting, and that's how in some cases they can persist for years.

Some studies indicated that the HLA type of the fetal cells (HLA is the most variable family of genes in our genome because they encode an important part of the immune system; these genes are responsible for our ability to recognize different pathogens) circulating in the mother may affect the mother's risk of later developing auto-immune disorders, systemic sclerosis in particular.

There are beneficial effects, too:
"As previously noted, fetal cells that appear to have differentiated into organ-specific phenotypes have been found in some patients with thyroid or liver damage, suggesting a role for fetal microchimerism in repair (Srivatsa et al. 2001; Stevens et al. 2004) [1]."
In other words, these fetal cells could have been recruited to the damaged tissue in an attempt to repair the lesions.

What about the effects of maternal cells circulating in the fetus?
"Fetal acquisition of maternal cells may have even more dramatic consequences on later fetal health than fetomaternal transfer does on maternal health [1]."
Maternal cells have been found in numerous fetal tissues: fetal liver, lung, heart, thymus, spleen, adrenal, kidney, pancreas, brain, and gonads. Maternal cells are able to migrate to an organ and differentiate into a local phenotype -- something that is truly intriguing, as the mechanism by which this happens could help inform organ regeneration research. Numerous autoimmune disorders like neonatal lupus, for example, have been associated with high levels of maternal microchimerism. However, it's not clear if the higher concentrations have a pathogenic effect and therefore cause the disease or, instead, are an effect of the disease. It could be that, for example, the maternal cells are recruited in higher concentration in an attempt to repair the damaged tissues. For example, one of the studies discussed in [1] found a beneficial role of maternal microchimeric cells in type I diabetic pancreas.

[1] Gammill HS, & Nelson JL (2010). Naturally acquired microchimerism. The International journal of developmental biology, 54 (2-3), 531-43 PMID: 19924635


Comments are moderated. Comments with spam links will be deleted and never published. So, if your intention is to leave a comment just to post a bogus link, please spare your time and mine. To all others: thank you for leaving a comment, I will respond as soon as possible.