What did you tell your mother? Communication between the embryo and the mother

Written by: Alireza Fazeli, Professor of Clinical Genomics and Personalized Medicine at the University of Tartu Institute of Biomedicine and Translational Medicine.

We have all been tormented by mosquitos in the summer time and thought “what a nuisance these creatures are”. But did you know that you and the mosquito had something very fundamental in common? Yes, you, and me of course, were literally parasites at one point of our life. We were completely dependent on someone else for every bodily requirement. I am talking, of course, about the nine months or so we spent inside our mothers.

For all practical purposes, an embryo is a parasite feeding on the ample bounty of the mothers being. Even though half of it is made out of the mother’s body, it develops an identity of its own before it attaches to the mother’s body in the fifth day of fertilization. If any other parasite tries to attach to a human being, the defences of the body would launch a serious attack on that parasite. We would do everything possible to prevent the parasite attaching and holding on. But uniquely, the embryo gets no such opposition from the legions of defences in the human body. The main question I try to answer in my studies is: why?

Scientists have noticed that this lack of response has something to do with the endometrium, the topmost layer of the uterus. In addition to changing dramatically during the menstrual cycle, the endometrium also changes in very specific ways when it is expecting an embryo. This time period, which can last 4 days, is called the “window of implantation”.

One way to explain the reason the endometrium would identify the embryo as a non-threat and change itself to accept the embryo is a series of communication between the embryo and the mother. In other words, we, at the tender age of five days after fertilization, communicated to our mother that we are not a dangerous parasite, but a potential child trying to attach to our mothers. Finding “what did you tell your mother” to convince her that you are not a threat is my main research aim.

To learn this language, we face a daunting obstacle. How do we check if there is a communication between the embryo and the mother? It would be horribly unethical to collect samples of implanted embryo. Luckily there is a scientific method of mimicking the conditions in a uterus just before implantation. The Transgeno research group in Tartu University started to use cancer cells that mimic the characteristics of trophoblast, the outer cell layer of embryo, and cells that mimic the endometrium. They labelled the “trophoblast” cells to track down messages from the embryo into the “endometrium” and found that there indeed is a communication between the embryo and the endometrium and the mode of this communication is RNA. (1, 2)

The Transgeno group then started to look more closely towards the actual method of this communication. We were interested in the potential of extracellular vesicles. Extracellular vesicles are the cargo ships of the cell world. Tiny, about ten thousandth of a millimetre big, these are bags that travel between cells carrying essential goods. We isolated the extracellular vesicles produced by the trophoblast and added them to the endometrium. We were able to see the same communication happening when we just used extracellular vesicles of trophoblast instead of the trophoblast itself. The good thing about this finding is that, in the future, we can use extracellular vesicles to increase the rate of implantation by artificially signalling the endometrium.

To sum up, one third of all failed pregnancies happen due to failure of implantation. If the reasons for this condition are discovered, we can increase the conception rate tremendously. In countries with fledgling birth rates, this would be a huge help to stabilize the population.

Communication between the embryo and the mother is one of the research topic at ERA Chair of Translational Genomics at the University of Tartu (European Union’s Horizon 2020 research and innovation program under grant agreement No 668989).

1 Deciphering embryo-maternal communication; the dynamics of first contact between progenitor and progeny. Kasun Godakumara, Masoumeh Es-haghi, Keerthie Dissanayake, Freddy Lättekivi, Andres Salumets, Ülle Jaakma and Alireza Fazeli. ISEV2019 Abstract Book. J Extracell Vesicles. 2019;8(Suppl 1):1593587. Published 2019 Apr 23. doi:10.1080/20013078.2019.159358.

2 Tracking and capturing of bioorthogonal labelled RNA carried by extracellular vesicles during maternal–embryo communication Masoumeh Es-haghi; Annika Häling; Freddy Lattekivi; Stoyan Tankov; Victoria James; Tamer Nafee; Sulev Koks; Alireza Fazeli. ISEV2018 abstract book. J Extracell Vesicles. 2018;7(Suppl 1):1461450. Published 2018 Apr 30. doi:10.1080/20013078.2018.146145.

The proofreading of this article was funded by the European Regional Development Fund through Estonian Research Council.