Gestational Diabetes Mellitus Alters Placental Precursor mRNA Splicing

Area of Science:

• Molecular Biology
• Genetics
• Reproductive Medicine

Background:

• Gestational diabetes mellitus (GDM) is hyperglycemia during pregnancy with poor maternal and neonatal outcomes.
• Molecular mechanisms underlying GDM complications are poorly understood.
• Previous studies focused on GDM placental transcriptomics, neglecting mRNA splicing.

Purpose of the Study:

• To investigate the impact of GDM on placental mRNA splicing.
• To identify regulatory mechanisms of GDM-associated splicing changes.
• To explore potential therapeutic targets for GDM.

Main Methods:

• RNA sequencing of placental samples from Norwegian and Chinese cohorts.
• Differential splicing event analysis and pathway enrichment.
• Splicing factor motif analysis and CLIP-sequencing (CRICKETS).
• Silencing of SRSF10 in placental cells.

Main Results:

• Thousands of differential splicing events were identified in GDM placentas.
• Enriched pathways included metabolic and diabetes-related pathways.
• SRSF10 was identified as a key regulator, binding to misspliced exons.
• Silencing SRSF10 replicated GDM-associated missplicing.

Conclusions:

• Splicing dysregulation is a critical factor in GDM pathogenesis.
• SRSF10 plays a key role in GDM-associated placental missplicing.
• Targeting SRSF10 may offer a therapeutic strategy for GDM.