Western professors Daniel Hardy and Tim Regnault are hopeful one day adult onset diseases such as obesity, diabetes and cardiovascular disease will be treated even before a child is born.
Professors Tim Regnault and Daniel Hardy study how conditions in the womb can trigger adult-onset diseases, such as obesity, diabetes and cardiovascular disease. ptiontexthere
As professors in the Schulich School of Medicine & Dentistry’s Department of Obstetrics and Gynecology, with cross appointments in Physiology and Pharmacology, the pair are sharing an interest in fetal development to learn what happens when before birth or, as they call it, fetal programming.
“The idea is there are a lot of people who study adult-onset diseases, looking at exercise, nutrition, diet, family history – all the known risk factors,” says Hardy, who came to Western last year from the University of Texas Southwestern Medical Center.
“What Tim and I are looking at in a sense, aside from the known risk factors, is the fetal origins for these diseases. This is the idea that what happens in-utero could influence you post-natally, and more importantly in adulthood.”
In-utero insults (or influences), such as infection, low oxygen, diet, cholesterol, body composition and stress, will lead to an environment that programs the fetus to alter its metabolic programming, which can have unfavourable outcomes after birth.
All of these alone or in combination during pregnancy could then affect fetal growth and development, leading to low birth weight and greater susceptibility to diseases as an adult.
“All throughout life you are under various influences, be it environmental, diet or exercise, and that is continually changing your metabolism and having a long-term affect on your longevity,” says Regnault, who with Hardy is a scientist at the Children’s Health Research Institute (Lawson Health Research Institute). “What we’re doing is looking at that little bit of window of life, before all that starts.”
Classically, scientists have looked postnatally. But over the last 20 to 30 years, development of the fetus has played a bigger role.
“Understand, you go through more milestones as a fetus than you do during your whole lifetime,” says Regnault, adding it is important to slowly progress the metabolism of low-birth-weight babies.
“In utero, if you’re growing in a bad environment, your body is saying ‘this is all I’m going to get or see, so I’m going to change my metabolism to survive and live in this environment’,” says Regnault, who taught at the University of Colorado before Western.
“It doesn’t know that when it pops out it’s going to get this mismatch between what it saw in utero and what is now potentially available. The greater the mismatch, the greater the chance of disease, based on what the body was programmed to do and what it is actually allowed to do.”
The recommendation would be to follow a “slow curve and catch-up more gradually,” as opposed to attempting to accelerate growth.
Hardy says while the link has been made, it’s not understood when in fetal development the programming occurs. The idea behind the research, which has been boosted by a $725,000 Canada Foundation for Innovation grant to overhaul lab space, with financial support also from Schulich, is to pinpoint when this programming actually takes place.
“If we can pinpoint when these insults manifest and change the programming, it would influence perhaps when we should screen or profile pregnant mothers for these things,” says Hardy. “It’s difficult to intervene in some cases, but there may be some safe methods to intervene. One could be cholesterol. The debate is ‘can you intervene’? Can you give cholesterol-lowering drugs to pregnant women? That’s a real debate.”
“You have to be careful in understanding there’s no magic bullet here,” adds Regnault. “More our work is basically looking and understanding the underlying mechanism that leads to these conditions so that maybe in the future we can go down the path and generate some sort of therapeutic intervention either prenatally or most likely postnatally.”
In the meantime, the two researchers are anxiously awaiting their new 1,800-square-foot laboratory, to be fully operational by year’s end, which will boost the research capacity not only for them but for their entire Schulich team.
“This is a good indication of how Western and Schulich are investing in their future and how they believe in what we are doing,” says Regnault. “We didn’t come for the infrastructure, we can for the people. You don’t need a shining tower to have good ideas, but it helps.”