Mothers’ Diabetes May Induce Premature Aging Of Neural Tissue Leading To Birth Defects

A significant number of foetuses (300,000 to 400,000) each year from diabetic mothers develop neural tube defects, when the specific tissue that ultimately leads to formation of the brain and spinal cord does not form properly. As a result, there is a miscarriage, or the baby undergoes profound disability.

After conducting studies on mice, researchers from University of Maryland School of Medicine (UMSOM) have successfully identified the mechanism behind the structural birth defects: they say that it is due to premature aging of the neural tissue, which halts its growth before it has produced sufficient cells to complete formation of the neural tube.

Nearly 60 million women of birthing age throughout the world have diabetes. Even when managed with insulin, and blood glucose levels are kept in check, maternal diabetes can lead to permanent damage to the foetus.

The study was published in Science Advances and was conducted by the UMSOM Centre for Birth Defects Research.

Does Diabetes Affect Pregnancy?

Although diabetes is a chronic disease that is generally associated with the elderly population, the present-day modern diabetes epidemic in young individuals is predominantly caused by obesity and lack of physical activity. Simultaneously, several ageing-related diseases are largely impacted by diabetes, and it is known that high blood sugar levels tend to induce or enhance premature ageing of the embryo.

One of the researchers went on to say that for several decades it was hypothesised that premature ageing (known as senescence) was occurring in the foetuses of women with diabetes and was, in part, leading to an inducement of birth defects. It only recently that researchers have had access to the technology and tools to successfully test their hypothesis.

Diabetes and Pregnancy Birth Defects

Finding the exact mechanism of maternal diabetes and birth defects in the foetus is the foremost step when it comes to identification of ways to prevent abnormalities from occurring. In the study, researchers successfully delayed the ageing process in the tissue through the use of a cancer drug, allowing the neural tube to form completely in mouse pups that were born from mice with mutations that mimic diabetes.

The findings indicate that more specialised therapies could be successfully developed to prevent miscarriages or the onset of birth defects in babies born from diabetic mothers.

First, the team of researchers demonstrated that the neural-tube tissue in 8-day-old mouse pups from mothers with diabetes contained several markers of premature ageing. These markers were lacking in pups from mothers that had no diabetes. The team then found that those cells with premature-ageing markers secreted a flurry of chemical signals that resulted in the death of neighbouring cells.

In the next stage, researchers successfully treated the pups that were born to diabetic mothers with the cancer drug, rapamycin, which is known to prevent the release of toxic chemical signals by the prematurely ageing cells. They eventually found that mouse pups that were treated with rapamycin possessed neural tubes that were completely formed similar to those that were found in pups born from mothers that did not have diabetes.

According to a researcher, this drug made the senescent cells to behave normally. On the downside, rapamycin affects too many diverse cell processes and can be potentially toxic. Hence, it would not be a viable treatment option when it comes to preventing the neural-tube defects in human infants.

The researchers’ next step was to check if birth defects of the kidney and heart found in foetuses of diabetic mothers are the result of the identical senescence mechanism. If found to be true, it would suggest that the researchers could develop a single treatment that is more specialised to these developmental processes to eventually prevent this range of birth defects.

On A Final Note

Because mothers with diabetes give birth to children with 5 times the birth defect rate in comparison with the general population, and because the incidence of diabetes is increasing significantly, it is quite imperative for researchers to develop ways and means to prevent disability and promote healthy births.