Researchers in the DeBerardinis Lab at CRI developed a new method last year to study metabolism directly in developing mouse embryos and uncovered new information about how the placenta and embryo use nutrients to grow, uncovering an answer to the development of childhood metabolic diseases.

These findings will help scientists paint a clearer picture of how inborn metabolic diseases interfere with fetal development and could provide opportunities to treat fetal metabolic defects during pregnancy.

“We think these findings will open up an entirely new way to study metabolism,” said Ralph DeBerardinis, M.D., Ph.D., CRI Professor and Howard Hughes Medical Institute Investigator. “It should be possible to activate or inactivate metabolic pathways of interest, at just the right time and location during development.”

Approximately halfway through mouse gestation, equating to 9-12 days after conception, the placenta begins to transfer nutrients and oxygen to the embryo to supply metabolic pathways that promote growth and organ formation. This period has been difficult to observe in utero using conventional methods. As a result, the basic biology of how the placenta and embryo use nutrients to grow and develop is still poorly understood.

“We know proper metabolic control is essential for healthy development, because defects in metabolic enzymes can cause problems in the way the body forms,” Dr. DeBerardinis said. “But we generally do not know why or how. So, we need practical ways to study metabolism during fetal life.”

Surprisingly, researchers found that glucose metabolism also changes rapidly, but only in the embryo. Between days 9 and 12 of gestation, the embryos get better and better at using glucose to supply metabolic pathways that produce energy and building blocks for growth. In contrast, the placenta’s use of glucose is relatively stable over the same period. And by day 12 of gestation, the team could observe distinct patterns of nutrient use in different developing organs, with the brain and heart prominently using glucose as a fuel and the developing liver preferring to use glutamine, an amino acid.

The findings demonstrate that distinct fuel preferences are evident among the developing organs early in fetal development.

“The finding that fetal tissues have specific fuel preferences early in development is important because it suggests specific metabolic pathways that are critical for the formation of individual fetal organs. This may indicate why genetic defects in metabolic enzymes can affect the development of one tissue but not another,” said Ashley Solmonson, Ph.D., the postdoctoral fellow in the DeBerardinis lab who led the study.