<b>Gestational Diabetes Mellitus Alters Placental Pre-mRNA Splicing</b>
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posted on 2025-11-18, 00:10 authored by 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<p dir="ltr">Gestational diabetes mellitus (GDM) is defined as hyperglycemia first identified during pregnancy and can lead to adverse maternal and neonatal outcomes. The molecular mechanisms leading to these outcomes are currently poorly understood. While transcriptomics of GDM placentas has been previously studied, the effect on pre-mRNA splicing remains largely unknown. This study explores the impact of GDM on placental splicing and identifies its regulatory mechanisms. Using RNA-sequencing data from European and Chinese cohorts, we uncovered thousands of differential splicing events. Pathway enrichment analysis revealed significant associations with metabolic and diabetes-related pathways. Splicing factor motif and CLIP-seq analyses highlighted SRSF10 as a key regulator in this process, with its binding enriched at mis-spliced exons. Silencing SRSF10 in placental cells mirrored GDM-associated mis-splicing in key genes. These findings underscore splicing dysregulation as a critical process in GDM pathogenesis, suggesting that targeting SRSF10 could be a potential therapeutic approach to mitigate the deleterious effects of GDM.</p>
Funding
This study was supported by a grant from the Joint Research Fund of the Hebrew University of Jerusalem and Kaplan Medical Center (TS & MS); and by the Israel Science Foundation (ISF 462/22; MS); the Alon Award from the Israeli Planning and Budgeting Committee (PBC; MS);
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