Gestational diabetes can cause a multitude of complications in the offspring, but to date, the reasons are incompletely understood. A new study, exploring a foundational step on the process of building proteins from genetic material, called splicing, reveals that this process is affected, 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, that 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 one day 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 newborn, 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.
Placental Molecular Changes
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.”
"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." -Dr Schiller
Implications for Offspring
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 here.
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