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Science interrupted ... by fetal microchimerism

This time on Science interrupted I’m going to talk to you about how my adventures in science were interrupted by fetal microchimerism. And why that is so totally cool.

For a little backstory, a lot of what I’m going to talk about requires you to have some fundamental knowledge about the placenta (if you want some more detailed reading, I highly recommend The Evolution of the Human Placenta). After conception happens, the placenta is the first organ that begins to form1,2. Most of the first trimester of pregnancy is devoted to placental growth3 - while the placenta continues to grow with the fetus throughout pregnancy, the placenta “takes over” and starts interacting with the maternal system. The placenta is a massive endocrine organ4 that transfers nutrients, oxygen, hormones, and waste products between mom and fetus5–8. But in addition to transferring these products between mom and fetus, the placenta can also transfer fetal cells into the mom’s body! (I’ve said it once, I’ll say it again, the placenta is probably the coolest organ you know nothing about)

The cells that the placenta sends into mom’s body are called fetal microchimeric cells (meaning cells from two different sources that live together in one individual - in this case, cells from mom and fetus living together in mom’s body). If you (or someone you know) has ever talked about finding out about their fetus’s health or sex through a blood test, you are already familiar with this concept. The fetal cells that are in mom’s circulatory system can be extracted in a sample of mom’s blood, and then separated in the lab so that genetic analyses and tests can be run on the fetus before it is born.

Until recently, it was assumed that after birth these cells were kicked out of mom’s body and she went back to being made up of only her own cells. In fact, one of the primary functions of the immune system after birth is to remove the remaining fetal microchimeric cells from mom’s body9 (and, interestingly, it is this immune response that is thought to be responsible for the baby blues and postpartum depression10). But, the immune response isn’t perfect and fetal cells (from every pregnancy mom has ever experienced) often remain in mom’s body for the rest of her life.

Wild.

A few years ago, some members of my lab wrote an amazing paper on this topic11. Since I had my daughter, I’ve spent a fair amount of time being fascinated by the fact that her cells are still living in me - and probably have been in conflict with my own cells. Her cells and mine aren’t 100% genetically related, so it is possible that things that are good for her cells might not be good for mine and vice versa. In this paper, they talked about the positive and negative effects that fetal microchimeric cells can have on mom’s health long term. Fetal microchimeric cells have been found in the brains, thyroids, breast tissue, and immune systems of moms DECADES after they have given birth. These areas can confer benefits and help fetuses survive after birth: brains coordinate behavior, so fetal cells here can influence mom’s attachment to, caretaking of, and investment in the baby; thyroids control body temperature, so fetal cells here can increase mom’s body temperature to help keep the fetus warm after birth (after birth, babies aren’t great at maintaining their own body temperature, so finding a way to make mom do this helps them save energy while maintaining a healthy body temperature); breast and mammary tissue produce milk, so fetal cells here can increase milk production to ensure that the baby has access to nutritious food; and the immune system coordinates immune functioning, so fetal cells here can ensure that the fetus is tolerated during pregnancy (remember that pregnancy is the only time that an immune system doesn’t try to get rid of cells that are not the same as the mom - conception, implantation, and pregnancy generally are immunological processes). The paper also goes on to talk about how when maternal and fetal interests are not aligned, this can cause problems in the mom’s body. Some of these problems can cause things like cancer and autoimmune diseases.

Shortly after my daughter was born, I eagerly watched to see if I could find evidence of her microchimerism in my own body. And boy did I ever. My normal body temperature has increased by at least one degree since she was born, helping to keep her warm when I hold her but also causing me to overheat frequently. My mammary cells went into overdrive creating milk, ensuring that she had enough to eat but also causing me discomfort and oversupply issues (thankfully I haven’t had to deal with blocked ducts or mastitis, but these are frequent issues caused by oversupply and potentially by microchimeric cells). I haven’t seen any evidence that my immune system is more active since she was born, but I also haven’t been sick throughout my pregnancy and postpartum periods. Maybe this is evidence enough that her cells are motivating my immune system to behave differently.

Finally, while I haven’t seen evidence that her cells are changing the way my brain works to make me love and care for her more than I would otherwise, I can’t deny the science behind this. I think it is important to say here that even though microchimeric cells might be one of the reasons behind the love that mothers feel for their children, they are not the only reason nor do they make the emotion any less real or powerful. If anything, the fact that microchimeric cells influence this speaks to how interconnected our bodies and brains are. Our biology influences how we think and feel. It only makes sense that this would be another place that microchimeric cells influence our behavior. People often say you don’t know the true extent of love until you are looking at your child, and this sentiment echos what we know about fetal microchimeric cells in women’s brains.

In case you are interested, here are some of the articles that I read and thought about while writing this.

1. Maltepe, E. & Fisher, S. J. Placenta: the forgotten organ. Annu. Rev. Cell Dev. Biol. 31, 523–552 (2015).

2. Maltepe, E., Bakardjiev, A. I. & Fisher, S. J. The placenta: transcriptional, epigenetic, and physiological integration during development. J. Clin. Invest. 120, 1016–1025 (2010).

3. Burton, G. J. & Jauniaux, E. What is the placenta? Am. J. Obstet. Gynecol. 213, S6.e1, S6–8 (2015).

4. Murphy, V. E., Smith, R., Giles, W. B. & Clifton, V. L. Endocrine regulation of human fetal growth: the role of the mother, placenta, and fetus. Endocr. Rev. 27, 141–169 (2006).

5. Bell, A. W., Hay, W. W., Jr & Ehrhardt, R. A. Placental transport of nutrients and its implications for fetal growth. J. Reprod. Fertil. Suppl. 54, 401–410 (1999).

6. Lager, S. & Powell, T. L. Regulation of nutrient transport across the placenta. J. Pregnancy 2012, 179827 (2012).

7. Freyer, C. & Renfree, M. B. The mammalian yolk sac placenta. J. Exp. Zool. B Mol. Dev. Evol. 312, 545–554 (2009).

8. Hay, W. W., Jr. Placental transport of nutrients to the fetus. Horm. Res. 42, 215–222 (1994).

9. Kolialexi, A., Tsangaris, G. T., Antsaklis, A. & Mavroua, A. Rapid clearance of fetal cells from maternal circulation after delivery. Ann. N. Y. Acad. Sci. 1022, 113–118 (2004).

10. Kendall-Tackett, K. A new paradigm for depression in new mothers: the central role of inflammation and how breastfeeding and anti-inflammatory treatments protect maternal mental health. International Breastfeeding Journal vol. 2 6 (2007).

11. Boddy, A. M., Fortunato, A., Wilson Sayres, M. & Aktipis, A. Fetal microchimerism and maternal health: a review and evolutionary analysis of cooperation and conflict beyond the womb. Bioessays 37, 1106–1118 (2015).

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