������Ƶ

The placenta is an essential organ for the developing fetus, both protecting the fetus from potentially harmful components in the blood and transferring nutrients needed for growth and development. But it remains largely a mystery.

“For a long time, the placenta was ignored because it was seen only as a temporary organ, and that’s been to our detriment,” says Eliza McColl, a PhD student in the lab of Professor Micheline Piquette-Miller in U of T’s Leslie Dan Faculty of Pharmacy. “As much as we can describe changes that occur in the placenta and hypothesize about the effects they might have, we can’t really understand what those changes could mean if we don’t have a detailed understanding of the placenta’s baseline function.”

This lack of knowledge about the placenta is one of the major gaps in studying the health of pregnant people. Piquette-Miller and her team are helping to fill this knowledge gap. They are studying how the placenta functions by examining transport proteins that regulate how nutrients, drugs and other molecules cross the placenta to the fetus. Much of her research has focused on whether infection and inflammation during pregnancy alter these transporters, which may ultimately change a fetus’s exposure to these substances.

For example, if a pregnant parent takes a drug considered safe in pregnancy but then experiences a viral infection or inflammatory condition such as preeclampsia, the expression of drug transporters in the placenta may change and alter the safety or efficacy of the drug. The research adds far more nuance to the discussion of what is safe and unsafe in pregnancy.

Piquette-Miller’s team has also contributed to a relatively new body of work suggesting that while the placenta itself is temporary, changes to it may lead to lifelong effects on offspring, including neurodevelopmental or metabolic disorders.

During McColl’s PhD research, she focused on transporters that allow amino acids essential for the fetus’s developing brain to cross the placenta – specifically whether infection or inflammation change the expression of these amino acid transporters and whether these changes are related to neurodevelopmental disorders in the offspring.

Using animal models, she found that amino acid transporters decreased after infection and that the offspring had altered levels of amino acids in the brain, and she identified that the cell signaling pathways that regulate these transporters are altered by infection. The results, 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 by therapeutics to reverse the nutrient deficits in the offspring.

“It's an interesting field of research that goes beyond describing the bare minimum of understanding the placenta, which is all that we’ve had for so long,” says McColl. “This is particularly 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 key gap in pharmaceutical research: women and pregnant people have often been excluded from clinical trials and medical research. If conditions present differently between the sexes, diagnoses or differences in drug side effects or efficacy 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 about how they respond to medications or how they present with different conditions or diseases,” says McColl. “It’s definitely a risk to include pregnant people in clinical trials, but we also have to give people the tools they need to make decisions about their own health.”

In the case of the COVID-19 vaccine, pregnant people were excluded from many clinical trials, but they were allowed to decide for themselves whether to get the vaccine after it was approved. Many did choose to receive the vaccine, which provided the data to show that the vaccine is safe and effective in pregnancy – as reflected in current vaccine guidelines.

“I hope that the COVID-19 vaccine has been a turning point in showing the value of letting pregnant people exert agency and volunteering to receive drugs or vaccines in trials because that is currently a huge gap in the research,” says McColl.