Mother

During pregnancy, the mother and the baby communicate in a variety of ways. For instance, signals from the fetus crucially involved in the initiation of labor and delivery. One important means of such signaling is the passage of packages called exosomes; very small particles release from every cell. These are only about 30 to 150 nm in diameter, and travel in both directions between mother and fetus. Exosomes contain chemicals which act as signals between maternal and fetal tissues.

Thus they serve as a biological indicator of the functional state of the tissue they arise from. Earlier, the researchers found that exosomes from the fetal side tell the mother’s body; that the baby has reached maturity. This triggers off labor and delivery. Now the researchers wanted to take this forward, finding out how far it extends and of what it is capable. Their aim was to investigate its usefulness in monitoring; and possibly treating some fetal conditions like preterm labor.

Exosome passage and function

To do this they had to do two things: isolate and track the exosomes. The current study look at exosome passage and function; by staining them using two fluorescent dyes that attach to the cellular membranes. This would let them glow on confocal microscopy. One dye is red fluorescent protein (RFP) tdTomato, while the other was the RFP-tdTomato/artificial green fluorescent protein (GFP) cyclic recombinase-reporter molecule found only in the tissues of the fetus.

The mouse model use for the study shows a red color if the conditions are normal. However, if cyclic recombinase is present, the tdTomat excised by the enzyme, leading to a green color. This helps detect the passage of cells and exosomes from the fetal side alone, since the GFP construct not found in maternal tissue.

As a result, the fetal tissues (fetal membranes and placenta) and exosomes positive for the RFP.  The presence of fetal exosomes in the mother’s uterine tissue test by immunostaining with the CD81 molecule which targets exosomes via antibody binding, and RFP tdTomato expression confirmed. An antibody to RFP tdTomato added to the mother’s blood to bind the RFP tdTomato-positive fetal exosomes, causing them to precipitate.

Peritoneal cavity of the mother

There about 35% fetal exosomes in the mother’s plasma. Those that positive for RFP tdTomato isolated from maternal blood and uterine tissue. Another set of exosomes to which the recombinase enzyme had add injected into the peritoneal cavity of the mother. This crossed the placenta and caused the removal of the RFP tdTomato from the construct in the fetal tissues which therefore became green.

Fetal exosomes positive for GFP also found in maternal blood. This study shows that exosomes travel freely between the fetal and maternal side of the placenta, and carry cell signals that communicate both maternal and fetal physiological messages. On arrival, they regulate the functional activity of the target tissue on both sides. Maternal exosomes can lead to functional alterations in the fetal tissues.

Fetal exosomes indicate the health and level of development of the fetus. Exosomes trafficked freely as part of the paracrine system of communication during pregnancy, in fact. The researchers think this could lead to their use as minimally invasive biological indicators of fetal health, for fetal monitoring via maternal blood samples. They can also used as drug carriers, or transporters of other useful molecules, to the fetus. Their chief recommendation is that they can used to advance research into the fetus without any invasive testing.