English physician David Barker, M.D., Ph.D., noticed an interesting phenomenon when he studied babies born during the Dutch famine in the mid-1940s. He discovered that these babies — although small for their gestational age — had a much higher incidence of diabetes, heart disease and obesity when they grew up.
This idea, that the health of a woman during pregnancy could affect whether her child develops chronic diseases as an adult, was coined the “Barker Hypothesis” in the early 1990s. During the past decade, more scientists have confirmed this hypothesis through pregnancy studies on substances ranging from high and low amounts of protein to excess amounts of nutrients such as glucose and fat.
Maternal obesity and diabetes also have been associated with both small and large babies and a subsequent increased risk of obesity, diabetes and metabolic syndrome in adults. But the mechanisms underlying these increased risks are not well understood and likely involve both genetic and environmental factors.
Kelle H. Moley, M.D., professor of obstetrics and gynecology, and Jean E. Schaffer, M.D., associate professor of medicine, have received a grant from the Children’s Discovery Institute to investigate whether mice born to mothers with type 1 and type 2 diabetes and obesity will develop metabolic syndrome.
“What we expect to find is that exposure in utero does predispose these offspring to high blood pressure, metabolic syndrome and other cardiac problems,” Moley says. “We want to determine if this is due to environment or genetics.”
Moley, a reproductive biologist, will implant one-day-old embryos and five-day-old embryos from healthy mice into mice with metabolic disorders resembling type 1 diabetes and type 2 diabetes. She then will study the effects of maternal diabetes on the implantation and development of the embryos.
After the mice are born, Schaffer, who researches heart muscle and lipid metabolism, will follow them until they are 20 weeks old. Twenty weeks old in a mouse is the equivalent of middle age in humans.
During the 20 weeks, Schaffer will measure weight, serum leptin levels, changes in body composition and insulin and glucose levels. She also will use mini X-ray machines to measure their body fat and a tiny tail cuff that measures blood pressure.
“We’re trying to pinpoint the vulnerable period in development at which metabolism plays a role in the long-term outcome,” Schaffer says.
Moley and Schaffer hope that their work will provide insight into the growing problem of obesity and cardiovascular disease in children and help women plan healthier pregnancies.
“The benefit would be that moms realize that they’re putting their children at risk if they’re obese or have metabolic syndrome when they get pregnant,” Moley says. “We want them to understand that they can reduce their children’s risk if they wait to get pregnant until they’re in better shape.”