New Data Shows Gene Expression at Different Stages of Pregnancy

While the exterior features of a woman can alter throughout pregnancy, scientists are surprisingly ignorant about the interior biological changes that take place.

Data on immune cells and biological changes (gene expression) in pregnant women at various periods before and during pregnancy are presented in a new Northwestern Medicine study, which was published on June 5^th, 2023 in the journal Frontiers in Immunology.

The team of researchers demonstrated how pregnancy induces progressive changes in the maternal immune system during each trimester, discovering that neutrophil activation, one type of immune cell, changes dramatically.

They did this by using RNA sequencing and computational methods to calculate the measurements of different activated types of immune cells in the blood.

We estimated the proportions of different cell types in blood. One cell type, called neutrophils, just shot up during pregnancy. We see it went up during the first and second trimesters and then went down a tiny bit by the third trimester and postpartum. This suggests to us that neutrophils probably are doing something important during pregnancy.”

Damini Jawaheer, Research Associate Professor, Rheumatology, Feinberg School of Medicine, Northwestern University

There have been many studies examining immune cell behavior during pregnancy, and those that have done so have not used a pre-pregnancy baseline. This limited the knowledge scientists could glean from such investigations because it is impossible to determine exactly what changes take place during pregnancy in the absence of a pre-pregnancy comparison.

But establishing a pre-pregnancy baseline requires identifying women who will become pregnant in the future, which is challenging and presents a challenge.

The scientists studied healthy women who planned to become pregnant throughout their pregnancies in the new study. The only individuals included in the outcomes had healthy pregnancies that ended in term deliveries.

To comprehend biological changes broadly, scientists focused on gene expression rather than genes themselves. Not all genes are expressed simultaneously: To metabolize food, the insulin gene, for instance, activates briefly when food is consumed.

After gathering blood samples, the researchers utilized those to determine how much RNA each gene produced before pregnancy and during each trimester, showing how strongly a gene was expressed. A unique alteration in one type of cell called neutrophils was one startling discovery.

According to Jawaheer, the role of neutrophils during pregnancy is not well understood. They are one of the first immune cells to react when a cell is assaulted by bacteria and viruses, according to scientists. The most prevalent form of immune cell in the blood is neutrophils.

According to Jawaheer, her findings dispute several other studies that suggested neutrophils might have a harmful effect on pregnancy and instead suggests a possible protective benefit.

Jawaheer stated, “We think they may have a beneficial role because otherwise we would not see such a huge increase in those cell numbers among healthy women in term pregnancies. There needs to be more work done because we can’t say much about the function of the neutrophils from what we studied.”

With the help of these findings, Jawaheer hopes to gain a better understanding of why rheumatoid arthritis (RA) naturally subsides during pregnancy. The researcher claimed that the study brings her one step closer to resolving the key research topic of her lab: How does an incurable illness like RA simply disappear during pregnancy?

Previously, Jawaheer had to come up with her own definition of what is “normal” to determine what would be problematic in RA pregnancy since there was no established “normal reference.”

“This was just a first pass with very high-level findings. We have also collected other samples at different time points, and we will look at those next. Perhaps there is some cell types other than neutrophils that play an important role in pregnancy that we weren’t able to see because we were looking at a mixture of all the cells in blood together,” Jawaheer added.

Jawaheer concluded, “We also hope this normal reference can help people doing research on diseased pregnancies like preeclampsia because you need to know what ‘normal’ is to understand what’s abnormal in a diseased pregnancy. And a ‘normal’ that includes a pre-pregnancy baseline was totally missing until now.”