Study Uncovers Molecular Disruptions in Placenta Caused by Gestational Diabetes - Video

A breakthrough in pregnancy research is changing our understanding of how gestational diabetes impacts mother and child. Scientists from the Hebrew University of Jerusalem, with collaborators at Kaplan and Wolfson Medical Centers, have uncovered a new molecular mechanism linking gestational diabetes mellitus (GDM) to pregnancy complications. Their study, published in Diabetes, focused on a critical step in gene expression called RNA splicing, which determines how genetic instructions are assembled into proteins in the placenta.

Gestational diabetes is a type of diabetes that develops during pregnancy when the body cannot produce enough insulin to manage the increased blood sugar. It usually appears in the second or third trimester and can lead to complications like high birth weight, preterm birth, and increased risk of type 2 diabetes later in life for both mother and child. Early diagnosis and proper management through diet, exercise, and sometimes medication can help protect maternal and fetal health.

Researchers analyzed RNA sequencing data from European and Chinese pregnancy cohorts, identifying hundreds of errors in RNA splicing within placentas affected by gestational diabetes. These errors were particularly concentrated in genes that regulate metabolism and diabetes-related pathways. The main culprit appears to be a protein called SRSF10, known for its role in RNA splicing. Laboratory experiments confirmed that blocking SRSF10 in placental cells caused disruptions that mirrored those found in GDM pregnancies, implicating it as a master regulator of placental function.

The study’s methodology involved comparing RNA splicing patterns in placental tissues from healthy and GDM pregnancies, using advanced sequencing techniques to map molecular changes. Functional studies where SRSF10 was suppressed reinforced the critical role of this protein in maintaining normal placental gene expression. These findings suggest that targeting SRSF10 could someday help prevent or lessen gestational diabetes complications for newborns.

The research reveals why babies born to mothers with GDM are at higher risk for complications such as abnormal birth sizes, pre-term deliveries, and long-term metabolic problems. By unraveling how disrupted splicing impairs placental function, the work offers new hope for interventions. Understanding SRSF10’s role could lead to therapies that improve pregnancy outcomes and protect offspring from diabetes-related health issues even later in life.

REFERENCE: Eden Engal, Adi Gershon, Shiri Melamed, Aveksha Sharma, Hadas Ner-Gaon, Shiri Jaffe-Herman, Yuval Nevo, Alena Kirzhner, Oren Barak, Edi Vaisbuch, Gillian Kay, Anne Cathrine Staff, Ralf Dechend, Florian Herse, Tal Shay, Maayan Salton, Tal Schiller; Gestational Diabetes Mellitus Alters Placental Precursor mRNA Splicing. Diabetes 2025; db250333. https://doi.org/10.2337/db25-0333