New evidence on the link between maternal diabetes and neural tissue damage in the fetus that can lead to profound disability or miscarriage has been uncovered.
Globally, around 300,000 to 400,000 fetuses per year from mothers with diabetes develop neural tube defects—when the tissue that eventually forms the brain and spinal cord fails to form properly.
Even when controlled with insulin, and blood sugar levels are kept mostly in check, maternal diabetes can cause permanent damage to the fetus.
Now using studies in mice, researchers have identified the mechanism behind these structural birth defects.
They say they are due to the neural tissue aging prematurely, halting its growth before it has made enough cells to finish forming the neural tube.
The study was led by University of Maryland School of Medicine (UMSOM) in the US.
Peixin Yang, professor of obstetrics, gynaecology and reproductive sciences director, said: “Although diabetes is a disease generally associated with an older population, the modern diabetes epidemic in young people is largely fuelled by obesity and inactivity. At the same time, many aging-related diseases are impacted by diabetes, and we now know that high blood glucose seems to induce or enhance premature embryonic aging.
“For many decades, our hypothesis was that premature aging, known as senescence, was occurring in the fetuses of mothers with diabetes, and was, in part, inducing these birth defects. It was only recently that we have had the tools and technology to be able to test our hypothesis.”
Finding the precise mechanism for how maternal diabetes leads to these and other kinds of birth defects in the fetus is the first step to identifying a way to prevent these abnormalities from occurring.
In the study, the researchers were able to delay the aging process in the tissue by using a cancer drug, allowing the neural tube to fully form in mouse pups born from mice with mutations mimicking diabetes.
Their findings suggest that more specialised therapies could be developed to prevent miscarriages or birth defects in babies born from mothers with diabetes.
First, the research team showed that the neural tube tissue in eight-day old mouse pups from mothers with diabetes contained markers of premature aging.
These markers were not found in pups from mothers that did not have diabetes. Researchers then found that the cells with premature aging markers secreted a flurry of other chemical signals that caused the neighbouring cells to die.
Next, the researchers treated the mouse pups from mothers with diabetes with the cancer drug rapamycin, known to prevent the toxic chemical signals from being released by the prematurely aging cells.
They found that mouse pups treated with rapamycin had neural tubes that were fully formed like those found in pups born from mothers without diabetes.
“This drug essentially made the senescent cells behave normally,” said Dr Yang. Unfortunately, rapamycin affects too many other cell processes and can be toxic, so it would not be a viable treatment for preventing neural tube defects in human infants.
