Everyone is susceptible to infection, including pregnant women. If a pregnant woman develops as bacterial respiratory infection that settles in the lungs as pneumonia for several days in a row, the toxins secreted by the bacteria can be incredibly harmful to the fetus.
A new study shows how the mother, child and placenta each defend themselves against such a bacterial infection.
The research shows that the mother reacts in one way, the fetus in another way and the placenta in a third way. All three responses develop incredibly dynamically during the first 24 hours following infection, and this probably avoids acute injury to the fetus.
The discovery also shows how the fetus gives priority to protecting its own brain when the mother becomes ill.
“This is an exciting discovery, which provides groundbreaking knowledge about how a pregnant woman’s body and placenta and the fetus defend themselves against infections,” explains a researcher behind the study, Signe Schmidt Kjølner Hansen, Postdoctoral Fellow, Zierath Group, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark.
The research has been published in Nature Communications.
Bacterial toxins are extremely harmful to the fetus
A gram-negative bacterial infection produces toxins called lipopolysaccharides located on the surface of the bacteria’s cell membranes.
In a respiratory infection, lipopolysaccharides are spread via the blood in the pregnant woman’s body, and this signals the immune system to go on high alert.
Lipopolysaccharides cause the immune system to increase the body temperature, which helps to suppress the bacterial infection.
However, this is serious for a pregnant women. In fact, lipopolysaccharides can be so dangerous that a severe infection in the mother’s body can kill the fetus. Signe Schmidt Kjølner Hansen and colleagues therefore aimed to investigate how the pregnant woman, the fetus and the placenta respond to acute bacterial infections.
“For example, previous research has shown that the children of pregnant women who have severe bacterial infections during pregnancy have an increased risk of developing several disorders later in life, such as cardiovascular diseases or nervous system and mental disorders,” says Signe Schmidt Kjølner Hansen.
Investigating the responses of the mother, the fetus and the placenta
The researchers exposed pregnant mice to lipopolysaccharides in the lungs during the third trimester and then attempted to mimic the quantities of lipopolysaccharides that are normally excreted from the body in connection with an infection.
Over the next 24 hours, they then examined how the mother’s immune system, the placenta and the fetus responded to lipopolysaccharides by taking samples from various organs over time and examining changes in the transcription of genes.
Transcription is the translation of DNA into proteins and shows how cells and organs adapt to the environment: for example, whether proteins from the immune system are activated or proteins responsible for growth are switched off so that the cell can focus on more vital processes.
“We investigated whether the mother’s inflammation and illness end up being transmitted to the fetus and how the placenta can regulate the transport of hazardous substances between the mother and the fetus,” explains Signe Schmidt Kjølner Hansen, adding that the question has not yet been investigated as thoroughly over several periods of time and in as many different organs as the researchers did in this study.
“We expected that the mother would get slightly ill and have a fever and that the fetus would react in the same way,” she notes.
Fetus denied access to the placenta
However, events did not unfold as the researchers expected. First, they found that the placenta temporarily strengthened its barrier function and thus minimised the possibility of lipopolysaccharides and inflammatory alarm signals reaching the fetus.
The placenta did this already after five hours, when it began to upregulate the production of proteins that make the placenta a more impenetrable filter between the mother and the fetus.
This increased barrier function of the placenta disappeared after approximately seven hours, when the mother’s lipopolysaccharides and inflammation levels in the blood were also declining, and a total barrier between mother and fetus was therefore no longer needed.
“What was surprising was that there was no immune response at all in either the maternal or the fetal part of the placenta, which should defend itself but does not. Instead, it just physically cuts off harmful substances reaching the fetus, and this is interesting because no one has before captured such a dynamic and precise response in the placenta and fetus. This provides new insight into how the placenta adapts to defend the fetus against various toxins,” explains Signe Schmidt Kjølner Hansen.
Fetus gives priority to protecting the brain
The second discovery was perhaps even more interesting because the researchers had expected that the fetus would have an immune response that was very close to that of the mother, but it did not.
Instead of putting the immune system into overdrive, the fetus’s liver began to break down various types of fat and carbohydrate.
This response is very similar to what is known from fasting, in which the body begins to burn fat to use the components of the fatty acids in other necessary places in the body.
Although the placenta creates an impenetrable barrier, the fetus can sense that the mother is infected with a bacteria, which may mean that she will not eat as much in the coming period. Therefore, the fetus adjusts to the fact that there may be a period without external nutrition.
During that period, it has to fend for itself, and the fetus does this by consuming its limited fat stores.
“This is a novel mechanism that can affect the development of the brain immediately after birth if the mother was ill for a period leading up to the birth. During that period, the fetus can mobilise fat tissue to survive without nutrition,” says Signe Schmidt Kjølner Hansen, elaborating that it is also interesting to determine which types of fatty acids the fetus mobilises during the infection.
“The most upregulated fatty acids are essential omega-3 fatty acids, more precisely docosahexaenoic acid, which is essential for brain development. The fetus is completely dependent on receiving docosahexaenoic acid from the mother’s diet, since people cannot produce this fatty acid. When the fetal liver mobilises all its stored docosahexaenoic acid, even if the mother is sick and not eating as much and the placenta has created a temporary barrier between the mother and the fetus, the fetal brain can continue to develop so that the brain is ready for the child to be born shortly afterwards and to process many new stimuli,” concludes Signe Schmidt Kjølner Hansen.
