Science interrupted ... by the third brain

This time on Science interrupted I’m going to talk to you about how my adventures in science were interrupted by the third brain1 -- the almighty placenta

So why placentas? Back story - I proposed my dissertation a few weeks ago. Going through that whole process (which in and of itself is a monster project) has given me a ton of opportunities to watch a ton of cool talks and read a ton of cool books and articles about the placenta, pregnancy, and postpartum periods. It has also given me a unique (and strange) opportunity to watch my research interest play out in my own life -- I am a new parent of a spunky little opinionated 7-month-old.

So here are some cool facts I’ve been learning about the placenta, the coolest organ that you know pretty much nothing about. This post mainly deals with the functions and structure of the placenta. In another blog post, I’ll talk about all the cool stuff the placenta does but first we have to talk about the basic biology of the placenta to set the stage.

The placenta is the interface of all maternal and fetal interactions throughout the course of pregnancy. Need some resources so the fetus can grow big and strong? The placenta’s got your back! Due to this extremely intimate connection, most common opinions of pregnancy (and by extension, common views of the placenta) are seen as cooperative. But this isn’t the whole story -- in fact, the placenta is genetically identical to the fetus2 and is predominated by paternally expressed genes3. This means there are MANY opportunities for pregnancy to be more conflictual than cooperative.

With the exception of marsupials (kangaroos, koalas, opossums, wombats) and monotremes (platypus and echidnas), all of the mammals that we know and love are placental. But, even within eutherian mammals (the official name for all mammals that are not marsupials and monotremes), not all placentas are created equal (this book4 gives a pretty good overview if you want to learn more than what I’m going to talk about below - the book is so good, I’m currently reading it for the third time). 

Before the placenta develops, the conceptus (aka fertilized egg before implantation) is accompanied by the yolk sac, allantois, chorion, and amnion5

The yolk sac provides nutrients to the embryo before the structures that will become the placenta attach to the uterine wall but the yolk sac also helps get the embryonic development started and produces proteins, cells, and other functions that are necessary for development6. Once the structures that become the placenta develop and attach to the uterine lining, the yolk sac shrinks and stops playing as large of a role in development7 (though it does continue to help transfer nutrients by helping to form the umbilical cord). The allantois, chorion, and amnion are what eventually become the placenta that we think of8. The allantois forms the vascular portion of the placenta (think blood vessels and umbilical cord), the amnion is the membranes that surround the fetus (when you think of water breaking during pregnancy, you are thinking of the amniotic fluid in the amnion), and the chorion is the membranes closest to the maternal tissues (it is outside the amnion and helps keep the fetus and amnion safe during pregnancy)9

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However, even though eutherian mammals share these four tissues, the actual structure of the placenta varies greatly. This also means that the intensity of genetic conflict in these species also varies greatly. The aspect of placental structure that influences the intensity of genetic conflict is the separation of maternal and fetal tissues. Which, more accurately, deals with the number of maternal tissues that are eroded during implantation or how deeply the placenta invades into maternal tissues4,10. The more erosion, the “easier” it is for the placenta to get nutrients from maternal blood, the more potential for manipulation and conflict between maternal and fetal interests.

There are three categories of placental structure: epitheliochorial, endotheliochorial, and hemochorial.

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Image from10

In epitheliochorial placentas, all three layers of maternal tissues and three layers of fetal tissues remain intact so there is very little opportunity for fetal manipulation of resource transfers. The fetal tissues just don’t have access to the maternal blood supply. Lucky pig, cow, and horse moms.

In endotheliochorial placentas, some of the maternal tissues are eroded during implantation so that the placenta has more access to the maternal blood supply but does not have direct access. This situation leads to the possibility for some fetal manipulation but, since it isn’t unlimited access, the maternal system can prevent extreme manipulation and extraction of resources from happening. So we can have some empathy for dog and cat moms.

The fun stuff happens with the hemochorial placenta (and by fun, I mean that in the science way - this is super weird and interesting). In hemochorial placentas, all of the maternal tissues are eroded away during implantation. This means that the fetal tissues are the only thing separating maternal and fetal blood, and this paves the way for major fetal manipulation and extraction of resources from the maternal system, which the maternal body has few strategies for keeping these extractions in check. Humans have this type of placenta, which suggests that humans also experience a huge amount of genetic conflict during pregnancy. It isn’t all sunshine and roses like we’ve been led to believe.

Placentas also differ in how they attach themselves to the uterus4,11, and this also influences the potential for genetic conflict and manipulation between maternal and fetal interests. In diffuse placentas, the placenta completely surrounds the fetus and attaches almost entirely to the uterine wall. In cotyledonary/ multicotyledonary placentas, the placenta is dispersed around the fetus and attaches to the uterine wall in multiple different locations. In zonary placentas, the placenta forms either a partial or complete band around the fetus and can only attach to the uterine wall closest to the banded section. Finally, in discoid placentas, the placenta is a flat and round, disk-like-looking organ that attaches itself to the uterine wall. If you look at the image below, discoid placentas have the most surface area that can attach to the uterine wall. More surface area means more opportunities to interact with maternal tissues and potentially gain more resources.

Humans have discoid, hemochorial placentas. In other words, humans have invasive placentas with a lot of surface area to interact with the maternal blood to gain resources necessary for growth.

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Image from11

So you might be wondering what this has to do with psychology. I promise I’ll get to that in another post. But the important thing here is that humans have incredibly invasive placentas. And it is this characteristic of human placentas that make it possible for them to do everything that they do. They send hormones, insulin, and fetal cells into the maternal body to change her physiology and behavior, and some of these effects last for DECADES after pregnancy (especially those of fetal microchimeric cells). Each pregnancy, whether it is completed to term or not, brings new fetal microchimeric cells into the maternal body to influence her body and thinking. What is even wilder is that, if these cells make it into the reproductive cell line or cross over the placenta during a later pregnancy, it can have multigenerational effects12.

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Image from12

Sometimes, truth is so much cooler than fiction.

Stay curious my friends, 


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

1. Yen, S. S. The placenta as the third brain. J. Reprod. Med. 39, 277–280 (1994).

2. Burton, G. J. & Jauniaux, E. Development of the Human Placenta and Fetal Heart: Synergic or Independent? Front. Physiol. 9, 373 (2018).

3. Wang, X., Miller, D. C., Harman, R., Antczak, D. F. & Clark, A. G. Paternally expressed genes predominate in the placenta. Proc. Natl. Acad. Sci. U. S. A. 110, 10705–10710 (2013).

4. Power, M. L. & Schulkin, J. The Evolution of the Human Placenta. (JHU Press, 2012).

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

6. Donovan, M. F. & Bordoni, B. Embryology, Yolk Sac. in StatPearls (StatPearls Publishing, 2021).

7. Gough, K. J. & Riley, L. Week 5 ultrasound: What it would look like. (2009).

8. Herrick, E. J. & Bordoni, B. Embryology, Placenta. in StatPearls (StatPearls Publishing, 2020).

9. Gude, N. M., Roberts, C. T., Kalionis, B. & King, R. G. Growth and function of the normal human placenta. Thromb. Res. 114, 397–407 (2004).

10. PrabhuDas, M. et al. Immune mechanisms at the maternal-fetal interface: perspectives and challenges. Nat. Immunol. 16, 328–334 (2015).

11. Furukawa, S., Kuroda, Y. & Sugiyama, A. A comparison of the histological structure of the placenta in experimental animals. J. Toxicol. Pathol. 27, 11–18 (2014).

12. 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).