Exposure to environmental pollutants affects all of us in many ways — some that are well understood, and some that researchers are just beginning to explore.

One understudied area is the impact of pollutants like micro and nanoplastics. 

Thanks to $914,176 from the Canadian Institute of Health Research (CIHR), Memorial researchers will explore sex-specific vulnerability to these pollutants in depth. 

Co-investigators Drs. Lindsay Cahill, Department of Chemistry, and Ashlyn Swift-Gallant, Department of Psychology, along with their teams of student researchers, will conduct studies to determine why exposure to environmental pollutants in early life affects males and females differently.

Project motivation

The CIHR-funded project uses preclinical mouse models and was motivated by recent Memorial-led work funded by Health Canada, which measures micro- and nanoplastics in human pregnancies in Newfoundland and Labrador.

While still early, the preliminary results from the study suggest that plastic concentration may be higher in male placentas from complicated pregnancies, compared to female placentas and normal pregnancies.  

“The field of toxicology has been dominated by studies in male mice or has neglected to consider the impact of sex on exposure outcomes,” said Dr. Cahill. “We are committed to changing this, highlighting the importance of studying both sexes and how this will improve health outcomes for all.”

Both investigators bring unique and complementary expertise to the project, which promises to help address the global societal problem.

Dr. Cahill has extensive experience using biomedical imaging technologies to characterize development in mouse models of fetal distress, which will be integral in studying the consequences for brain development.

Dr. Swift-Gallant is an expert in sexual differentiation and transgenic models and behavioural tests, which will help disassociate the role of sex chromosomes and hormones.

XX vx. XY

Using mouse models of pregnancy, the research group is further studying the cause-and-effect relationships that are challenging to establish in humans.

To conduct the studies, the team separates the contributions of sex chromosomes (XX and XY) and sex hormones (ovaries vs. testes).

The project assesses social and communicative behaviours, using cutting-edge imaging technologies, including ultrasound, micro-computed tomography and nuclear magnetic resonance.

The combination will help the team explain how exposure to micro and nanoplastics impacts maternal health and will identify the mechanisms underlying the sex differences in fetal health outcomes. 

The researchers are also testing an intervention strategy to establish the benefits of a stable and active environment for improving pregnancy outcomes. 

“Our team has access to a unique array of tests to understand the mechanisms of sex differences and to translate the results to the clinic,” said Dr. Swift-Gallant.

“We are also very lucky to have access to a state-of-the-art animal facility,” said Dr. Cahill. “The Animal Resource Centre and the Animal Care and Veterinary Resources staff make it possible to conduct all of our experiments on site and use a transgenic mouse line that decouples sex chromosomes and gonadal hormones.”

Student successes

Student research findings were critical to the success of the grant and the continuing research, according to Drs. Cahill and Swift-Gallant.

The CIHR project also involves training graduate and undergraduate researchers who are developing expertise in animal handling, the use of transgenic models, biomedical imaging, behavioural testing, data processing, statistical analysis and knowledge mobilization.

“We made this mess, and I think we have a responsibility to research the consequences of microplastics exposure and how that might be expressed based on sex.” — Jayne Simmons

Over 50 per cent of the grant is dedicated to trainee funding.

The research team currently includes research associate Nadine Burry; PhD student Lucas Fowler; master of science student Haley Adams; master of science student Thomas O’Brien; bachelor of science honours student Evan Natsheh; and bachelor of science honours student Allison Spurrell. 

Mr. Fowler says the experience has been “immensely rewarding.”

“Working alongside Dr. Cahill and Dr. Swift-Gallant has allowed me to blossom as a person and scientist, refining my research interests and career goals,” he said.

The student researchers say that the combined passion for integrating female subjects and sex differences into the study design and statistical analysis is “deeply personal and strong.” 

“We want to advocate for the importance of investigating sex differences and emphasize that doing so can positively affect the generalizability of findings to all sexes, especially in a field where females are often unjustly excluded because of hormonal variability,” said Mr. Fowler.

Mr. Fowler’s preliminary work shows how exposure to nanoplastics negatively impacts maternal behaviours and results in differences between female and male fetuses in brain cytokine and steroid hormones. 

National collaboration 

An interdisciplinary team has been assembled to provide support to the ongoing research.

Dr. John Sled, imaging physicist at Mouse Imaging Centre at the Hospital for Sick Children, Toronto; Dr. Karl Jobst, analytical and environmental chemist at Memorial University; and Dr. John Kingdom, obstetrician and clinician scientist at Mount Sinai Hospital, Toronto, have come on board.

Patient partners with lived experience of pregnancy will provide their unique perspectives.

Jayne Simmons, a mother, math and science teacher and a patient partner working on the project, believes it would be premature to dismiss sex as a biological variable when considering possible consequences of microplastic exposure.

“We made this mess, and I think we have a responsibility to research the consequences of microplastics exposure and how that might be expressed based on sex, especially if that could affect young children,” she said.

Science is not linear

Scientific research is often thought of as a straight line from animal models to humans. 

In this case, the approach is intentionally bi-directional. The project emerged from human findings and the funded mouse work will provide a mechanistic understanding that can then be applied back to humans. 

“By identifying early biomarkers and mechanisms of toxicity, we hope the project will pave the way for developing sex-based precision therapies and establish guidelines to reduce exposure and prevent pregnancy complications caused by environmental plastic pollution,” said Dr. Cahill. 

The project builds on previous funding from New Frontiers in Research (Exploration) and Health Canada Environmental Health Research Contribution Program – Microplastics Stream. The transgenic model was procured under a previous CIHR Project Grant.

Learn more about how CIHR’s Sex and Gender-Based Analysis in Research Action Plan ensures that health research in Canada leads to sound science and reliable evidence that effectively addresses biological (sex) and sociocultural (gender and other identity factors) differences between diverse groups of people.