Jerusalem, 23 December, 2025 (TPS-IL) — Doctors have long known that gestational diabetes increases the risk of complications for both mothers and babies, but exactly how it harms the developing fetus has remained unclear. A new study from the Hebrew University of Jerusalem has now identified a previously unknown molecular process in the placenta that may help explain those risks and open new pathways for treatment.
Gestational diabetes mellitus is a form of diabetes that develops during pregnancy and is increasing in prevalence worldwide. It exposes the fetus to an abnormal metabolic environment, including elevated maternal blood glucose levels. The condition is associated with complications such as babies being born too large or too small, higher rates of caesarean and pre-term deliveries, and increased neonatal risks.
In addition, children born to mothers with gestational diabetes also face a higher likelihood of obesity and diabetes later in life.
Because diagnostic criteria and screening practices differ, there is no single global rate, but most estimates place gestational diabetes in about 10–15% of pregnancies worldwide, making it one of the most common pregnancy complications. When gestational diabetes is diagnosed, treatment focuses on controlling blood sugar levels to protect both the mother and the fetus.
The new research shows that gestational diabetes alters a fundamental biological process in the placenta known as RNA splicing. Splicing is the step in which genetic messages are assembled before being translated into proteins. According to the scientists, this is the first evidence that gestational diabetes causes widespread errors in placental RNA splicing, leading to hundreds of incorrectly assembled genetic messages that may impair how the placenta functions.
The study was led by Prof. Maayan Salton of the Faculty of Medicine at the Hebrew University of Jerusalem and Dr. Tal Schiller of the Hebrew University’s Kaplan Medical Center and Wolfson Medical Center at Tel Aviv University, together with PhD students Eden Engal and Adi Gershon. Researchers from other Israeli and European institutions were also involved. The findings were published in the peer-reviewed journal Diabetes.
Using advanced RNA sequencing data from both European and Chinese pregnancy cohorts, the researchers identified hundreds of consistent splicing alterations in placentas affected by gestational diabetes. Many of the affected genes play key roles in metabolism and diabetes-related pathways. The fact that the same molecular changes were observed across distinct populations suggests that disrupted splicing is a core feature of gestational diabetes rather than a secondary or population-specific effect.
A central discovery of the study was the role of a protein called SRSF10, which helps regulate RNA splicing. When the researchers experimentally reduced SRSF10 activity in placental cells, they observed the same splicing errors seen in gestational diabetes. This indicates that SRSF10 is not merely associated with the disease but may actively drive placental dysfunction. The identification of SRSF10 as a key regulator had not previously been linked to gestational diabetes or placental biology.
“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,” Schiller said.
Gestational diabetes is typically managed through diet, exercise, and insulin, approaches that control blood sugar but do not address underlying placental changes. By uncovering a direct link between maternal metabolism, placental RNA splicing, and fetal risk, the researchers say the study opens new avenues for interventions aimed at reducing both immediate complications and long-term health consequences for children.
First, the findings provide a clear biological explanation for pregnancy and long-term offspring complications that are not fully prevented by glucose control alone. Clinically, many women have well-managed blood sugar, yet their children still face higher metabolic risks. This study suggests that placental molecular dysfunction, not just blood glucose levels, may be driving some of those outcomes.
Second, the research identifies placental RNA splicing as a new therapeutic target. This opens the door to placenta-focused interventions aimed at correcting molecular errors rather than only managing symptoms.
Third, the identification of SRSF10 as a key regulator has practical research and drug-development implications. Because reducing SRSF10 activity reproduced gestational diabetes–like defects in placental cells, the protein could serve as a drug target or a pathway to modulate. Even partial correction of its activity might reduce placental dysfunction and downstream fetal risk.
Fourth, the findings may lead to new biomarkers for risk stratification. Splicing signatures or SRSF10-related molecular changes in placental tissue — or potentially in maternal blood — could help identify pregnancies at higher risk of complications, even when glucose levels appear well controlled.
Fifth, the study supports more personalized management of gestational diabetes. In the long term, clinicians may be able to distinguish between patients whose pregnancies are primarily affected by metabolic imbalance and those with pronounced placental molecular disruption, allowing for tailored monitoring and intervention strategies.
“By understanding how gestational diabetes disrupts the placenta at the molecular level, we can begin to imagine new ways to protect the offspring,” Salton said.
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