The placenta is an essential organ for fetal development, both protecting the fetus from potentially harmful components in the blood and transferring nutrients needed for growth and development. But that remains largely a mystery.
“For a long time, the placenta was ignored because it was considered only a temporary organ, and this was done to our detriment,” explains Eliza McColldoctoral student in the professor’s laboratory Micheline Piquette Miller at the Leslie Dan Faculty of Pharmacy at the University of Toronto. “While we can describe the changes that occur in the placenta and hypothesize what effects they might have, we can’t really understand what those changes might mean if we don’t have a detailed understanding of the basic function of the placenta.”
This misunderstanding of the placenta is one of the main shortcomings in the study of the health of pregnant women. Piquette-Miller and his team are helping fill this knowledge gap. They study how the placenta works by looking at transport proteins that regulate how nutrients, drugs, and other molecules travel through the placenta to the fetus. Much of her research has focused on whether infection and inflammation during pregnancy alter these transporters, which may ultimately alter fetal exposure to these substances.
For example, if a pregnant mother takes a drug considered safe during pregnancy but then experiences a viral infection or an inflammatory condition such as preeclampsia, the expression of drug transporters in the placenta may change and alter the safety or drug efficacy. The research adds many more nuances to the discussion of what is safe and dangerous during pregnancy.
Piquette-Miller’s team also contributed to a relatively new body of work suggesting that while the placenta itself is temporary, changes to it can lead to lifelong effects on offspring, including neurodevelopmental disorders. or metabolic.
During McColl’s doctoral research, she focused on transporters that allow amino acids essential to the developing brain of the fetus to cross the placenta – particularly if infection or inflammation alters the expression of these transporters. amino acids and whether these changes are linked to neurodevelopmental disorders in the offspring.
Using animal models, she found that amino acid transporters decreased after infection and offspring had altered levels of amino acids in the brain, and she identified that cell signaling pathways that regulate these transporters are altered by infection. The findings, which McColl is presenting at the American Society for Reproductive Immunology conference this week in Nashville, are the first step in understanding whether these changes could be targeted with therapeutics to reverse nutrient deficits in offspring.
“It’s an exciting area of research that goes beyond describing the bare minimum to understanding the placenta, which is everything we’ve had for so long,” McColl says. “This is especially important knowing that changes that occur in the placenta can actually impact the fetus after birth and throughout life.”
The COVID-19 pandemic has highlighted another major gap in pharmaceutical research: women and pregnant women have often been excluded from clinical trials and medical research. If conditions present differently between the sexes, diagnoses or differences in side effects or drug effectiveness in understudied groups could be missed. And many drugs have not been tested for use during pregnancy at all.
“We can’t effectively treat or properly care for people if we don’t have the data on how they respond to drugs or how they present with different conditions or illnesses,” McColl says. “It’s certainly a risk to include pregnant women in clinical trials, but we also need to give people the tools they need to make decisions about their own health.”
In the case of the COVID-19 vaccine, pregnant women were excluded from many clinical trials, but they were allowed to decide for themselves whether to receive the vaccine after it was approved. Many chose to receive the vaccine, which provided the data to show that the vaccine is safe and effective in pregnancy – as evidenced by current vaccine guidelines.
“I hope the COVID-19 vaccine was a turning point in showing the value of letting pregnant women exercise their agency and volunteer to receive drugs or vaccines in trials, because that is a huge gap right now. in research,” says McColl.