UCLA researchers lay groundwork to study effects of maternal diabetes on fetal metabolism and development

FINDINGS

UCLA scientists examined how exposure to higher levels of glucose alter fetal tissue metabolism, using a technique they pioneered to trace in utero carbon-13 in fetal tissues. Their paper, “Atlas of Fetal Metabolism During Mid-to-Late Gestation and Diabetic Pregnancy,” published in Cell today, reveals the impact of maternal hyperglycemia on fetal tissues.

BACKGROUND

If left unchecked, pregnant women with diabetes are more likely to face preterm birth and stillbirth — and they’re also more likely to deliver babies with congenital defects of the brain and heart. For example, diabetic mothers are five times more likely to give birth to a baby with cardiovascular defects. And to date, we do not know exactly why this happens. Today, UCLA scientists published a foundational study that opens the door to understanding how high levels of maternal blood glucose alters the metabolism of the fetus as it develops in utero.

Diabetic mouse model. | Image courtesy of Cesar Perez-Ramirez

METHOD

Using a mouse research model that mimics diabetic pregnancies, the UCLA team examined how exposure to higher levels of glucose altered fetal tissue metabolism. For this study, researchers pioneered the technique of in utero carbon-13 tracing in fetal tissues.

During mid-to-late gestation, they measured metabolites and metabolic activities in the placenta as well as in the fetal brain, heart and liver. Researchers targeted the most common metabolites for analyses and also conducted a broader, untargeted metabolomic analysis of metabolites that showed the greatest change in the course of development.

IMPACT

This research establishes a foundation for studying diabetic pregnancies and fetal health in utero, during mid-to-late-stage gestation, when vital organs are forming. The researchers show how metabolic profiles change as fetal organs develop in utero and how metabolic activity is altered in the fetuses of diabetic mothers. Their study has resulted in a wealth of data available for other researchers to mine, providing a useful resource for future studies of fetal metabolism, especially in the context of diabetes. These findings open the possibility for research to identify specific treatments so that diabetic mothers have a better chance of delivering healthy babies.

AUTHORS

The study’s first authors are Cesar Perez-Ramirez, a UCLA Broad Stem Cell Research Center trainee, and Haruko Nakano.  Senior authors are Junyoung Park, UCLA professor of chemical and biomolecular engineering; Atsushi Nakano, UCLA professor of molecular, cell, and developmental biology; and Heather Christofk, UCLA professor of biological chemistry. The corresponding authors are Heather Christofk and Atsushi Nakano. Other authors are Richard Law, Nedas Matulionis, Jennifer Thompson and Andrew Pfeiffer.

JOURNAL

The study is published online today in the journal Cell.