Cell Signaling Pathways and Diabetic-Induced Birth Defects

Pregnancy News

Obie Editorial Team

Researchers from the University of Maryland may have found a new means of reducing diabetic-induced birth defects. The study, published in the journal Science Signaling, claims cell signaling pathways may hold the key to a new supplement to reduce the risk of neural tube defects, in particular.

Neural tube defects (NTD) are a prevalent birth defect in the United States. About 1 out of every 33 infants is born with an NTD. Diabetic women are up to 10 times more likely to have a child with an NTD. Folic acid supplements are generally suggested before and during pregnancy to reduce the risk of NTDs, but they only work in about 70% of women and taking too much folic acid may be associated with increased risk of breast cancer in offspring later in life. Researchers believe a naturally-occurring substance called Thioredoxin may be the answer.

Cell signaling comes into play because increased levels of glucose in the blood activate the protein ASK1 (apoptosis signal-regulating kinase 1). Once the protein is active, it triggers cellular death by activating proteins called pro-cell death proteins. If ASK1 activity can be minimized or inhibited, the subsequent cellular death and increased risk of birth defects (particularly NTD) could be counteracted. This is where Thioredoxin comes into the picture.

The body naturally makes Thioredoxin. It is thought the protein offers antioxidant benefits, but researchers believe it could be just as effective as folic acid at reducing NTDs and possibly more effective in women who do not respond to folic acid. Animal studies show positive effects with Thioredoxin supplementation as do studies of human using samples taken from humans. There are some issues with supplement implementation, however.

There is very little research into the long-term effects and possible side effects of Thioredoxin supplementation. Researchers have no idea how the antioxidant works or how much is too much at this stage of research. Researchers how to nail down concrete information about Thioredoxin in future studies.

Source: Peixin Yang, Xuezheng Li, Cheng Xu, Richard L. Eckert, E. Albert Reece, Horst Ronald Zielke, and Fang Wang. Maternal Hyperglycemia Activates an ASK1–FoxO3a–Caspase 8 Pathway That Leads to Embryonic Neural Tube Defects. Science Signaling, 2013 DOI: 10.1126/scisignal.2004020.

Peixin Yang, Xuezheng Li, Cheng Xu, Richard L. Eckert, E. Albert Reece, Horst Ronald Zielke, and Fang Wang. Maternal Hyperglycemia Activates an ASK1–FoxO3a–Caspase 8 Pathway That Leads to Embryonic Neural Tube Defects. (27 August 2013) Sci. Signal. 6 (290), ra74.