During pregnancy, the woman’s cardiovascular system undergoes profound functional and structural changes. These changes ensure the supply of the foetus and placenta, but at the same time place high demands on the maternal vascular system. A recent study led by Ursula Hiden and Evelyn Jantscher-Krenn from the Medical University of Graz, published in the Journal of Physiology, sheds light for the first time on how a special group of cells, the so-called endothelial colony forming cells (ECFCs), changes during the course of pregnancy. Particular attention was paid to the influence of metabolism, inflammation and fetal sex.
Endothelial progenitor cells - key players in the adaptation of the vascular system
Endothelial progenitor cells circulate in the blood and contribute to the repair and formation of new blood vessels. ECFCs represent a subgroup that - when isolated from the blood - forms characteristic colonies in cell culture. While their diagnostic and therapeutic significance in the field of cardiovascular diseases is being intensively researched, little is known about their role in pregnancy.
In the recently published study, first author Marie-Therese Weiser-Fuchs examined ECFCs from the blood of healthy women in three different physiological stages: non-pregnant women, women in early pregnancy and women in late pregnancy. The samples were obtained as part of the PregWin cohort study, a translational research project at the University Hospital Graz, which makes it possible to investigate complex changes in the course of pregnancy in advance.
Cell growth and cell shape - significant differences depending on the stage of pregnancy
"When cultivating the ECFCs, there were clear differences in cell growth depending on the stage of pregnancy at which the cells were isolated. In late pregnancy, the success rate of ECFC isolation was highest at 61% and more cell colonies were formed per milliliter of blood," Marie-Therese Weiser-Fuchs explains her research. In addition, ECFCs from late pregnancy required less time for colony formation and formation of a so-called confluent monolayer, i.e. complete coverage of the growth surface by the cultured cells, which indicates increased mobilization and faster growth of ECFCs at this stage.
Microscopically, there were clear differences in the shape of the cells depending on their pregnancy status: While the ECFCs of non-pregnant women exhibited a spindle-shaped, elongated form, pregnant women, especially in late pregnancy, were dominated by rounder, polygonal cell shapes. These differences could be significant for their function, for example as an indication of different activation states or a kind of "cellular memory" of the environment.
Metabolism, inflammation and fetal sex influence ECFC behavior
In addition, significant correlations were found between the growth of ECFCs and metabolic and inflammatory parameters: increased colony formation was associated with increased lipid levels (cholesterol, triglycerides) and inflammatory markers (IL-6, E-selectin). These results suggest that ECFCs are not only influenced by local stimuli in the blood vessels, but also by systemic factors.
the influence of fetal sex was particularly interesting: in early pregnancy, the isolation of ECFCs from maternal blood was more frequent when the woman was expecting a girl. In late pregnancy, on the other hand, higher ECFC activity was associated with male fetuses. This previously undescribed correlation indicates a sex-specific control of the maternal vascular system, which may be mediated by differences in the placental secretome," explains Marie-Therese Weiser-Fuchs. The placental secretome refers to the entirety of substances released by the placenta.
The researcher also explains: "We also included a small group of women with gestational diabetes in our analyses. They showed a significantly increased ECFC colony formation compared to healthy control pregnancies. This could indicate a compensatory (i.e. balancing) activation of the vascular repair system." The data thus provide new clues for understanding the adaptive mechanisms of the vascular system in high-risk pregnancies.
Conclusion: new insights into the vascular system during pregnancy
The study shows how dynamically and precisely controlled restructuring processes of the vascular system take place during pregnancy. It is remarkable that the "programming" of ECFCs by metabolic and inflammatory changes during pregnancy persists even after isolation of the cells in culture. This cellular memory could be used clinically in the future. ECFCs have the potential to establish themselves as sensitive markers for the adaptation processes of the maternal vascular system and could therefore contribute to the early detection of high-risk pregnancies. A deeper understanding of their regulation could also open up new therapeutic approaches for the prevention and treatment of pregnancy-associated complications such as pre-eclampsia or gestational diabetes.
Profile: Marie-Therese Weiser-Fuchs
Marie-Therese Weiser-Fuchs is isolating and characterizing special endothelial cells (endothelial colony forming cells) from the blood of pregnant women as part of her dissertation. In doing so, she is attempting to investigate connections between the maternal metabolic state and the function of these cells. A further, partly related area of interest is research into human milk oligosaccharides and their role in maternal metabolism during pregnancy. The current focus is on research into the regulation of lipid and glucose metabolism during pregnancy, taking into account the influence of human milk oligosaccharides.