Bringing new life into research on the placenta

Charles McKenzie and Tim Regnault

The placenta is a powerhouse of an organ. Acting as the “life support” system for fetuses developing in their mother’s womb, it provides nutrients, oxygen, hormones and immune defense, and takes care of removing wastes.

External factors such as diet have a significant impact in the health of a placenta’s metabolism, impacting the way it, and the unborn it supports, develop and function, and potentially how the newborn develops and grows throughout his or her life outside the womb. Despite the role the placenta plays throughout this crucial time of development, there is currently no method available that allows direct measurement of metabolic processes in the placenta during early pregnancy.

Charles McKenzie, PhD, and Timothy Regnault, PhD, want to change this. As part of the National Institute of Health’s (NIH) Human Placenta Project, they have received $3.7 million CAD in funding over four years to develop a new technology based on magnetic resonance imaging (MRI) that will, for the first time, allow them to determine metabolism in the placenta and monitor changes in placental metabolism as pregnancy unfolds and when challenged by external maternal factors.

“We believe that with this technology, we will be able to see early signals of what is going wrong in the placenta that we currently don’t detect or are unable to see,” said McKenzie, associate professor in the Department of Medical Biophysics. “Using this technology, we hope to be able to identify where the problems are earlier, so clinicians and biomedical researchers can investigate possible treatments they should be using on a specific patient sooner than they can now.”

While this technology could potentially be used to look at a number of different external factors and diseases during the course of a pregnancy, McKenzie and Regnault will focus their project on life-long maternal consumption of the “Western Diet” — an energy-dense diet that is high in calories from sugars and simple fats.

This type of diet has been associated with negative changes in the placenta, setting up a pregnant mother’s children and grandchildren for a predisposition to heart disease, diabetes and obesity.

“We are focusing on the Western Diet because of its prevalence in our society,” said Regnault, associate professor in the Departments of Obstetrics & Gynaecology, and Physiology and Pharmacology. “Obesity rates are increasing, and we know this diet is being increasingly consumed, so there is potentially a greater number of people worldwide that are eating this diet — an exposure that may be having a negative impact upon the placental metabolism and later newborn metabolic disease risk that we need to be aware of.”

“The whole goal here is to differentiate the pregnancy that is going to be fine from the pregnancy that looks fine now, but in six weeks isn’t going to be,” added McKenzie.

McKenzie and Regnault have been working on this research for a few years, for this specific application. They are using hyperpolarized MRI, and this will be the first time any researchers have used this technology to work with pregnancy.

Scientists hyperpolarize pyruvate, a naturally occurring molecule used by all cellular life for energy, which boosts the signal of the pyruvate enough that MRI can detect the molecule. The hyperpolarized pyruvate is injected into maternal circulation through which it moves to the placenta — scientists can then scan the mother, generating an image of the placenta that can be used to assess its metabolism.

Regnault commends the NIH for having the foresight to invest such a large sum of money into placental research, explaining that without a placenta none of us would exist, yet we know so little about it.

“The consensus is that we still do not know how a normal placenta grows, and we don’t know the main key markers of early metabolic failure,” Regnault said. “You can spend a lot of money looking at every woman who is pregnant, but there’s probably no need to do that — you just need to be able to clearly identify the at-risk groups that may need to be looked after early in pregnancy, which is what we’re trying to do.”

McKenzie and Regnault are excited about the resources this grant will allow them to bring into their labs, and that it gives them the opportunity to become part of a consortium of sixteen other investigative groups spread across the United States, Canada and countries in Europe.

The grant is a unique form of NIH funding that is specifically listed as a cooperative grant, meaning all awardees will need to have teleconferences and in-person meetings with one another on a regular basis.

“When I completed my bachelor’s degree in physics more than 20 years ago, I didn’t see myself learning about fetal physiology and working with pregnant women,” McKenzie said enthusiastically. “It’s very exciting to be funded for something that is high-risk and long-term, where the results could potentially have an impact on many people.”