Smoking and a poor diet have long been known to harm unborn babies, but evidence on how exercise benefits pregnant women and their future children has been sparse. A new study shows that a pregnant woman who exercises releases a special protein in the placenta that has previously been shown to improve the metabolism of animal fetuses. Researchers are now trying to understand this mechanism so that pregnant women and their children can have a healthier and better life.
In 2015, 370 million people worldwide had type 2 diabetes, and this number is projected to increase to 630 million by 2045. The patterns of risk for both obesity and type 2 diabetes can originate from alteration in metabolism during critical windows of prenatal development. Since physical activity can keep people with type 2 diabetes virtually symptom-free, an international collaboration with researchers from the United States, Canada, Japan and Denmark has revealed whether the positive effects of physical activity can be transmitted from the mother to the child before birth.
“Our experiments show that exercise during pregnancy can influence which genes the child expresses – and this may therefore potentially prevent the onset of obesity, type 2 diabetes and other lifestyle-related diseases later in life. The study is important because we now know more about a new approach to obesity and type 2 diabetes focusing on preventing them from developing before the baby is born rather than treating the children for them once they are born,” explains Niels Jessen, Professor of Clinical Pharmacology, Department of Clinical Medicine, Aarhus University and Head of Research, Steno Diabetes Center Aarhus.
Greater activity in the placenta
Today, every fifth child or adolescent is overweight or obese and is at high risk of developing cardiovascular disease, type 2 diabetes or other lifestyle-related diseases in adulthood. Research has shown that obesity among women of reproductive age is a prominent risk factor for transmitting obesity to subsequent generations, but very little is known about how this actually occurs.
“Previous research indicates that dietary changes by pregnant women can affect the genes of the fetus and the baby’s health. How pregnant women who exercise affects the fetus has been less clear, but since strong epidemiological evidence indicates that regular exercise can prevent disease, we thought that the effect on the fetus might be similar,” says Niels Jessen.
The idea for the new study arose when Niels Jessen’s long-time collaborator Laurie J. Goodyear of the Joslin Diabetes Center at Harvard Medical School mentioned experiments showing that the offspring of physically active pregnant mice had better glucose and fatty acid metabolism than offspring from physically inactive pregnant mice.
“The physically active pregnant mice had more superoxide dismutase 3 (SOD3) in their blood than the inactive ones, and this therefore suggests that exercise increases the amount of SOD3, which in turn positively affect the fetus. The experiments also showed that SOD3 is produced in the placenta. We therefore think it could be exciting to determine whether we can find a similar connection among people,” explains Niels Jessen.
One of several cogs
The researchers therefore decided to measure placental SOD3 expression and secretion among 400 pregnant women . The SOD3 increased as the placenta grows and sometimes also after physical activity, confirming that people produce SOD3 in the placenta and that physical activity increases production.
“The experiments also confirm that, even though you have the same genes for life, other factors affect their expression and activity, including SOD3 produced by the mother, which works by upregulating and downregulating which genes are expressed in the child,” says Niels Jessen.
SOD3 creates epigenetic reprogramming, in which tiny chemical changes demethylate DNA, which affects the extent to which each gene is expressed. The more active the mother is, the more SOD3 increases the expression of the genes that create a healthy metabolism.
“SOD3 therefore helps to determine the child’s ability to metabolize glucose and fat – and thus probably also the risk of developing obesity and type 2 diabetes. Removing SOD3 eliminates the benefit of exercise, but SOD3 is probably only one of several cogs in this complex machine, and we do not yet know whether it is the most important one,” explains Niels Jessen.
Benefitting pregnant women and their children
The new results pave the way for further studies to better understand how exercise by pregnant women affects the health of their children. The researchers have identified SOD3 as one cog. They plan to discover the others that work with SOD3 to understand the overall underlying mechanism.
“Many researchers are working to crack the code to prevent obesity among children, but why some children develop obesity is still a mystery. The discovery of SOD3 may prove to be an important breakthrough, but we also know that the connections are complex – and that prevention is also more complex than many people imagine,” says Niels Jessen.
This study is just the beginning for the researchers. In addition to investigating why exercise increases the production of SOD3 and other proteins, they also plan to use Denmark’s excellent biobanks to try to confirm the same link as in mice between pregnant women who exercise and biological markers such as SOD3 indicating the child’s health.
“This is the long-term perspective, because linking these markers to a child’s metabolic health will probably also enable us to determine how this can benefit pregnant women and their children. In the future, we hope that we can continue research on screening women, thereby helping women whose children have a greater risk of developing obesity and type 2 diabetes to engage in exercise that can benefit the child already during pregnancy,” concludes Niels Jessen.
