HIGH GLUCOSE levels during pregnancy have detrimental effects on the developing fetus, by stopping the conceptus’ heart cells from maturing normally, reports new research from the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles (UCLA), Los Angeles, California, USA. The study, led by Prof Atsushi Nakano, UCLA Molecular Biology Institute, provides an explanation as to why babies born to women with diabetes are at a higher risk of developing congenital heart disease.
Maternal diabetes is the leading non-genetic risk factor attributed to congenital heart disease, but until now the precise effect of glucose on the developing fetus has not been understood. The research team began their experiment by culturing human embryonic stem cells in vitro and stimulating their differentiation into cardiomyocytes, the cardiac muscle cells. These cells were then exposed to varying levels of glucose to explore its effects on the cells’ growth. Cardiomyocytes exposed to low glucose levels matured normally, whereas those exposed to high glucose levels developed at a slower rate or failed to mature at all. It was found that, when developing in the presence of high glucose levels, heart cells over-activate the pentose phosphate pathway, generating an excess of nucleotides that subsequently inhibit cell maturation. The group replicated this research in vivo and reported similar findings in pregnant mice with diabetes.
This study highlighted the need for a healthy diet during pregnancy; an intervention as simple as a dietary change could limit the extent of cell proliferation and thereby coax them into forming mature cardiomyocytes. Prof Nakano explained “By depleting glucose at the right point in development, we can limit the proliferation of the cells,” and suggested that the findings could also lead to a more appropriate way of producing cardiomyocytes from stem cells. He concluded: “High blood sugar levels are not only unhealthy for adults; they’re unhealthy for developing fetuses. Understanding the mechanism by which high blood sugar levels cause disease in the fetus may eventually lead to new therapies.”