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Embryonal non-coding RNAs in the human placenta and the maternal circulation.

Subject Area Gynaecology and Obstetrics
Term from 2016 to 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 315156279
 
Final Report Year 2023

Final Report Abstract

In the placenta, there is the interface between the maternal and fetal organisms. On the fetal side, it is formed by the syncytiotrophoblast, which surrounds all placental villous tissue and is in direct contact with maternal blood. The syncytiotrophoblast has extremely versatile functions, including the transport of all necessary substances from the mother to the fetus and the removal of substances that need to be eliminated in the opposite direction. Additionally, it actively produces numerous hormones that are important for the development of the fetus and the adaptation of the maternal organism to pregnancy. It is also known that the syncytiotrophoblast releases particles of various sizes. In this project, we have focused on the smallest known extracellular vesicles (EV), which can be divided into two groups: exosomes and microvesicles. We have previously studied noncoding RNA (ncRNA) in trophoblast cells, which can regulate gene expression in cells. We have developed a model that allows us to isolate large amounts of EV by perfusing human placental tissue after birth in a special system, excluding other sources of EV than the placenta. We then examined the content of specific ncRNA and messenger RNA (mRNA) in placental tissue as well as in exosomes and microvesicles using RNA sequencing and identified thousands of different RNA molecules. We found that exosomes and microvesicles do not have identical RNA profiles. Some of the RNA molecules in the EV appeared to originate from trophoblast cells, while others came from the rest of the placental tissue. We could show that placental EV can be taken up by different target cells in the maternal organism, such as T lymphocytes, natural killer cells, endothelial cells, beta cells of the pancreas, stem cells, or microglia in the nervous system. There were differences in the uptake and effects of exosomes and microvesicles. We were able to transfect trophoblast-derived cell lines with ncRNA to mimic physiological placental EV. The EV secreted from these cell lines had significantly altered ncRNA contents, and they were incubated with potential target cells. Fluorescence-labeled EV and the RNA contained within them could then be detected in the target cells using PCR, flow cytometry, and two-photon microscopy. Depending on the presence of specific RNA molecules in the EV, various functions of the target cells were significantly influenced. This project clearly demonstrated that the fetus communicates with the maternal organism during pregnancy through EV from the placenta and can contribute to adapting it to the specific requirements.

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