How do embryos talk? | Institute of Biomedicine and Translational Medicine, University of Tartu

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Lossi 36, 51003 Tartu
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Contacts of UT units

Faculty of Arts and Humanities
Faculty phone: 
+372 737 5341
Faculty address: 
Jakobi 2, rooms 116–121, 51005 Tartu
  • Dean's Office
    Faculty phone: 
    + 372 737 5341
    Faculty address: 
    Jakobi 2, rooms 116–121, 51005 Tartu
  • Institute of History and Archaeology
    Faculty phone: 
    +372 737 5651
    Faculty address: 
    Jakobi 2, 51005 Tartu
  • Institute of Estonian and General Linguistics
    Faculty phone: 
    +372 737 5221
    Faculty address: 
    Jakobi 2, 51005 Tartu
  • Institute of Philosophy and Semiotics
    Faculty phone: 
    +372 737 5314
    Faculty address: 
    Jakobi 2, rooms 309–352, 51005 Tartu
  • Institute of Cultural Research
    Faculty phone: 
    (+372) 737 5223
    Faculty address: 
    Ülikooli 16, 51003 Tartu
  • School of Theology and Religious Studies
    Faculty phone: 
    +372 737 5301
    Faculty address: 
    Ülikooli 18–310, 50090 Tartu
  • College of Foreign Languages and Cultures
    Faculty address: 
    Lossi 3, 51003 Tartu
  • Viljandi Culture Academy
    Faculty phone: 
    +372 435 5232
    Faculty address: 
    Posti 1, 71004 Viljandi
Faculty of Social Sciences
Faculty phone: 
+372 737 5957
Faculty address: 
Lossi 36, 51003 Tartu
  • Dean's Office
    Faculty phone: 
    + 372 737 5900
    Faculty address: 
    Lossi 36, 51003 Tartu
  • Institute of Education
    Faculty phone: 
    +372 737 6440
    Faculty address: 
    Salme 1a–29, 50103 Tartu
  • Johan Skytte Institute of Political Studies
    Faculty phone: 
    +372 737 5582
    Faculty address: 
    Lossi 36–301, 51003 Tartu
  • School of Economics and Business Administration
    Faculty phone: 
    +372 737 6310
    Faculty address: 
    J. Liivi 4, 50409 Tartu
  • Institute of Psychology
    Faculty phone: 
    +372 737 5902
    Faculty address: 
    Näituse 2, 50409 Tartu
  • School of Law
    Faculty phone: 
    +372 737 5390
    Faculty address: 
    Näituse 20–324, 50409 Tartu
  • Institute of Social Studies
    Faculty phone: 
    +372 737 5188
    Faculty address: 
    Lossi 36, 51003 Tartu
  • Narva College
    Faculty phone: 
    +372 740 1900
    Faculty address: 
    Raekoja plats 2, 20307 Narva
  • Pärnu College
    Faculty phone: 
    +372 445 0520
    Faculty address: 
    Ringi 35, 80012 Pärnu
Faculty of Medicine
Faculty phone: 
+372 737 5326
Faculty address: 
Ravila 19, 50411 Tartu
  • Dean's Office
    Faculty phone: 
    +372 737 5326
    Faculty address: 
    Ravila 19, 50411 Tartu
  • Institute of Biomedicine and Translational Medicine
    Faculty phone: 
    +372 737 4210
    Faculty address: 
    Biomeedikum, Ravila 19, 50411 Tartu
  • Institute of Pharmacy
    Faculty phone: 
    +372 737 5286
    Faculty address: 
    Nooruse 1, 50411 Tartu
  • Institute of Dentistry
    Faculty phone: 
    +372 731 9856
    Faculty address: 
    Raekoja plats 6, 51003 Tartu
  • Institute of Clinical Medicine
    Faculty phone: 
    +372 737 5323
    Faculty address: 
    L. Puusepa 8, 50406 Tartu
  • Institute of Family Medicine and Public Health
    Faculty phone: 
    +372 737 4190
    Faculty address: 
    Ravila 19, 50411 Tartu
  • Institute of Sport Sciences and Physiotherapy
    Faculty phone: 
    +372 737 5360
    Faculty address: 
    Jakobi 5–205, 51005 Tartu
Faculty of Science and Technology
Faculty phone: 
+372 737 5820
Faculty address: 
Vanemuise 46–208, 51014 Tartu
  • Dean's Office
    Faculty phone: 
    +372 737 5820
    Faculty address: 
    Vanemuise 46–208, 51005 Tartu
  • Institute of Computer Science
    Faculty phone: 
    +372 737 5445
    Faculty address: 
    Narva mnt 18, 51009 Tartu
  • Estonian Marine Institute
    Faculty phone: 
    +372 671 8902
    Faculty address: 
    Mäealuse 14, 12618 Tallinn
  • Institute of Physics
    Faculty address: 
    W. Ostwaldi 1, 50411 Tartu
  • Institute of Chemistry
    Faculty phone: 
    +372 737 5261
    Faculty address: 
    Ravila 14a, 50411 Tartu
  • Institute of Mathematics and Statistics
    Faculty phone: 
    +372 737 5860
    Faculty address: 
    J. Liivi 2, 50409 Tartu
  • Institute of Molecular and Cell Biology
    Faculty phone: 
    +372 737 5011
    Faculty address: 
    Riia 23, 23b–134, 51010 Tartu
  • Tartu Observatory
    Faculty phone: 
    +372 737 4510
    Faculty address: 
    Observatooriumi 1, Tõravere, 61602 Tartumaa
  • Institute of Technology
    Faculty phone: 
    +372 737 4800
    Faculty address: 
    Nooruse 1, 50411 Tartu
  • Institute of Ecology and Earth Sciences
    Faculty phone: 
    +372 737 5835
    Faculty address: 
    Vanemuise 46, 51003 Tartu
Institutions
  • Library
    Faculty phone: 
    +372 737 5702
    Faculty address: 
    W. Struve 1, 50091 Tartu
  • Youth Academy
    Faculty phone: 
    +372 737 5581
    Faculty address: 
    Uppsala 10, 51003 Tartu
  • Institute of Genomics
    Faculty phone: 
    +372 737 4000
    Faculty address: 
    Riia 23b, 51010 Tartu
  • Museum
    Faculty phone: 
    +372 737 5674
    Faculty address: 
    Lossi 25, 51003 Tartu
  • University of Tartu Natural History Museum and Botanical Garden
    Faculty phone: 
    +372 737 6076
    Faculty address: 
    Vanemuise 46, 51003 Tartu
Support Units
  • Administrative Office
    Faculty phone: 
    +372 737 5606
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Centre for Entrepreneurship and Innovation
    Faculty phone: 
    +372 737 6339
    Faculty address: 
    Lossi 3, III floor, 51003 Tartu
  • University Office in Tallinn
    Faculty phone: 
    +372 737 6600
    Faculty address: 
    Teatri väljak 3, 10143 Tallinn
  • Estates Office
    Faculty phone: 
    +372 737 5137
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Finance Office
    Faculty phone: 
    +372 737 5125
    Faculty address: 
    Jakobi 4, 51005 Tartu
  • Grant Office
    Faculty phone: 
    +372 737 6215
    Faculty address: 
    Lossi 3, III floor, 51003 Tartu
  • Information Technology Office
    Faculty phone: 
    +372 737 6000, IT-help: +372 737 5500
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Human Resources Office
    Faculty phone: 
    +372 737 5145
    Faculty address: 
    Ülikooli 18, rooms 302 and 304, 50090 Tartu
  • Internal Audit Office
    Faculty address: 
    Ülikooli 17–103, 51005 Tartu
  • Marketing and Communication Office
    Faculty phone: 
    +372 737 5687
    Faculty address: 
    Ülikooli 18, rooms 102, 104, 209, 210, 50090 Tartu
  • Office of Academic Affairs
    Faculty phone: 
    +372 737 5620
    Faculty address: 
    Ülikooli 18, 50090 Tartu
  • Procurement Office
    Faculty phone: 
    +372 737 6632
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Rector's Strategy Office
    Faculty phone: 
    +372 737 5600
    Faculty address: 
    Ülikooli 18, 50090 Tartu
  • Student Council
    Faculty phone: 
    +372 737 5400
    Faculty address: 
    Ülikooli 18b, 51005 Tartu
  • University of Tartu Press
    Faculty phone: 
    +372 737 5945
    Faculty address: 
    W. Struve 1, 50091 Tartu
Other Units
  • University of Tartu Academic Sports Club
    Faculty phone: 
    +372 737 5371
    Faculty address: 
    Ujula 4, 51008 Tartu
  • Tartu Student Village
    Faculty phone: 
    +372 740 9959
    Faculty address: 
    Narva mnt 25, 51013 Tartu
  • Tartu Students’ Club
    Faculty phone: 
    +372 730 2400
    Faculty address: 
    Kalevi 24, 51010 Tartu
  • Tartu University Hospital
    Faculty address: 
    L. Puusepa 1a, 50406 Tartu
  • University of Tartu Foundation
    Faculty phone: 
    +372 737 5852
    Faculty address: 
    Ülikooli 18, 50090 Tartu
  • View all other units

How do embryos talk?

When did you start speaking? Conventional wisdom would suggest that it would be around the one-year old mark. The conventional wisdom could be off by quite a bit in this case. I believe that the first word of our lives was uttered even before we opened our eyes.

We have been talking since we were embryos. Yes, embryos do talk. The language is not well understood, and it is inaudible, but embryos do speak to their mothers even before implanting in the uterus. In fact, one big reason we are here is probably because we were such big talkers in utero.

Since the inception of in vitro fertilization in 1977, the rate of successful pregnancies has not increased beyond 50%. One of the biggest causes for the low success rate is the failure of the embryo to implant in the endometrium, the innermost lining layer of the uterus.

Scientists have been busy trying to come up with reasons for the low amount of implantation. One of the hypotheses trying to describe the phenomenon, posits that embryos and the endometrium communicate with each other and this communication, if successful, causes the endometrium to change chemically, physiologically and morphologically bringing about the “window of implantation” which leads to a successful implantation.

In the Transgeno research group lead by the University of Tartu professor Alireza Fazeli, we are very much interested in baby talk, that is embryo-maternal communication.

Since it would be highly unethical to test any actual human embryos for embryo-maternal communication, we have used a malignant cell-line based system to replicate the microenvironment immediately prior to embryo implantation.

This is an enlarged view of an embryo in the mother’s uterus. JAR cells were used to mimic the outermost cell layer of the embryo, while RL 95-2 cells were used to mimic the innermost lining layer of the uterus.
Image credit: Kasun Madhuranga Godakumara Godagedara

One cell type, JAR, was used to mimic the trophoblast, the outermost cell layer of the embryo and another cell type, RL 95-2, was used to mimic the endometrium. JAR cells were formed into a 3D structure called a spheroid to imitate a trophoblast better.

Testing the hypothesis that the messages used in the communication are in the form of RNA, we have labelled all the RNA in the trophoblast spheroids. Since we have labelled the living cells, the process is termed bio-orthogonal labelling. When we put the two cell types together, we could track the transfer of embryonic RNA from the trophoblast to the endometrium, demonstrating the validity of the hypothesis. We observed that not only some species of RNA are indeed transferred from the embryo to the endometrium, but also the endometrial RNA changes because of the transfer.

Then we looked into the method of message transfer. Naturally, we started from the extracellular vesicles – the cargo ships of the cell world. Extracellular vesicles or EVs are very small (about 100nm in diameter) packages containing lipids, proteins, and nucleic acids, that is DNA and RNA. Once considered as just cellular junk, EVs and EV research has become one of the hottest topics in the scientific world in recent years.

We isolated the EVs produced by the JAR spheroids and supplemented the endometrial cells. Interestingly, the EVs were able to produce an identical change in endometrial RNA compared to the actual JAR spheroids. EVs seemed to be a major component in the embryo-maternal communication mechanism.

An embryo is essentially a parasite. It might sound a little horrifying to consider it as such, but immunologically, biochemically and genetically speaking, an embryo is completely different from the endometrial cells. The maternal immune system should be rejecting them like any other parasite or bacteria. However, in successful implantation, i.e. when the embryo is of the adequate quality, the maternal immune system seems to be ignoring the embryo. This observation leads to a hypothesis that the embryos with a high potential of implantation would transmit a different message from a degenerated embryo.

Using the knowledge gained by the JAR spheroid-based embryo-maternal communication model, we have then tried to look for the differences in the messages transmitted from good quality and bad quality human embryo.

We used in vitro fertilized embryos. In vitro fertilized embryos are grown in bubbles of culture media. We collected the used or “conditioned” media from the embryos and isolated the extracellular vesicles released from the growing embryo. Then we supplemented the isolated EVs to endometrial cells. The results revealed that only the embryos that were of good quality were able to affect the pre-observed changes in endometrial cells.

These results are the foundation of a new understanding of the first communication between the embryo and the mother. A more comprehensive understanding would be useful in the future therapeutic and diagnostic applications.

Kasun Madhuranga Godakumara Godagedara is a specialist and PhD student at the Institute of Biomedicine and Translational Medicine at the University of Tartu. His background is in cell biology and biotechnology. He is currently involved in experimentation to decipher the methods and characteristics of extracellular vesicle mediated embryo-maternal communication.