Gestational diabetes can cause a multitude of complications in the offspring, but to date, the reasons were barely understood.
A new study, exploring a foundational ‘splicing’ step in the process of building proteins from genetic material, reveals that this process is affected by diabetes, altering how the placenta reads and processes genetic instructions.
Researchers found that in pregnancies affected by gestational diabetes, hundreds of genetic messages are assembled incorrectly, potentially disrupting how the placenta functions. They identified a key protein, SRSF10, which appears to contribute to the disrupted process.
When this protein was blocked in lab cells, the same errors seen in gestational diabetes appeared, suggesting that targeting SRSF10 could help mitigate the deleterious effects of gestational diabetes on the offspring.
New study uncovers an unknown mechanism linking gestational diabetes to pregnancy complications. Gestational diabetes mellitus (GDM), a form of diabetes that develops during pregnancy, has an increasing prevalence worldwide. GDM causes a disrupted metabolic environment for the fetus, including elevated blood glucose levels from the mother. This may result in immediate complications for the newborns, such as being born too large or too small for gestational age, more caesarean deliveries, pre-term deliveries, and more. . It also has long-lasting effects on the offspring, with higher risks for obesity and diabetes later in life.
A new study led by Prof. Maayan Salton from the Faculty of Medicine at the Hebrew University of Jerusalem and Dr. Tal Schiller from the Faculty of Medicine at Hebrew University, Kaplan Medical Center, and Wolfson Medical Center at Tel Aviv University, together with PhD students Eden Engal and Adi Gershon, reveals that gestational diabetes alters the placenta at the molecular level in ways never seen before.
Published in Diabetes, a leading journal in the field, the study found that GDM changes how the placenta processes its genetic messages. Using advanced RNA sequencing data from both European and Chinese pregnancy cohorts, the team discovered hundreds of alterations in how RNA molecules are “spliced”, the step that determines which protein instructions are ultimately produced. These changes were strongly linked to genes involved in metabolism and diabetes-related pathways.
A key finding centered on SRSF10, a protein that helps control RNA splicing. When researchers reduced the activity of SRSF10 in placental cells, the same molecular disruptions seen in GDM appeared. This suggests that SRSF10 may be a master regulator of placental function, and potentially a new therapeutic target for preventing pregnancy complications.
“By understanding how gestational diabetes disrupts the placenta at the molecular level, we can begin to imagine new ways to protect the offspring” said Prof. Salton. “Our findings bring us a step closer to that goal,” added Dr. Schiller. “By pinpointing the specific molecular players involved, like the SRSF10 protein, we can start thinking about how to translate this knowledge into real-world strategies to improve pregnancy outcomes.”
Gestational diabetes is typically managed through diet, exercise, and insulin, but its underlying biology has remained poorly understood. This research sheds light on how the metabolic changes observed in GDM can alter how genes are processed, opening new avenues for intervention.
The research paper titled “Gestational Diabetes Mellitus Alters Placental Pre-mRNA Splicing” is now available in Diabetes, and can be accessed at https://diabetesjournals.org/diabetes/lookup/doi/10.2337/db25-0333
Researchers:
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, and Tal Schiller
Institutions:
- Department of Biochemistry and Molecular Biology, The Institute for Medical Research Israel–Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem
- Department of Life Sciences, Ben-Gurion University of the Negev
- Info-CORE, Bioinformatics Unit of the I-CORE Computation Center, The Hebrew University of Jerusalem
- Department of Internal Medicine A, Kaplan Medical Center and Faculty of Medicine, Hebrew University of Jerusalem
- Department of Obstetrics and Gynecology, Kaplan Medical Center and Faculty of Medicine, Hebrew University of Jerusalem
- Institute for Clinical Medicine, Faculty of Medicine, University of Oslo
- Division of Obstetrics and Gynaecology, Oslo University Hospital
- Experimental and Clinical Research Center, a cooperation between the Max‐Delbrück‐Center for Molecular Medicine in the Helmholtz Association and the Charité ‐ Universitätsmedizin Berlin
- Max‐Delbrück‐Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin
- HELIOS Clinic, Department of Cardiology and Nephrology, Berlin
- Department of Diabetes, Endocrinology and Metabolism, Kaplan Medical Center and Faculty of Medicine, Hebrew University of Jerusalem
- Department of Diabetes and Endocrinology, The Edith Wolfson Medical Center, Holon, Israel, Affiliated to the Gray Faculty of Medical and Health Sciences, Tel Aviv University