Differential transcript usage in the placenta in early onset preeclampsia

Area of Science:

• Genomics
• Molecular Biology
• Obstetrics

Background:

• Early onset preeclampsia (EOPE) is a severe pregnancy complication linked to maternal and fetal health risks.
• Hypertension is the sole consistent symptom, complicating early detection of EOPE.
• Current molecular markers for EOPE are limited, with only FLT1 showing significant changes.

Purpose of the Study:

• To investigate differential transcript usage (DTU) in placental samples from women with and without EOPE.
• To identify novel molecular markers and pathways associated with EOPE pathogenesis.
• To validate identified DTU events in an independent cohort.

Main Methods:

• Differential transcript usage (DTU) analysis of four public RNA sequencing datasets comparing EOPE and control placental samples.
• Comparison with preterm placentas to distinguish age-related changes from EOPE-specific events.
• Experimental validation of selected DTUs in an independent patient cohort.

Main Results:

• Identified 43 DTU events in EOPE placentas across multiple datasets, with 3 attributed to placental age.
• Genes with DTUs were enriched in cell junction and cell membrane-associated pathways.
• DTUs in FLT4, ADGRG6, MXI1, and LCP1 were experimentally validated.

Conclusions:

• Transcriptional alterations are integral to the molecular mechanisms of EOPE.
• Validated DTUs in FLT4, ADGRG6, MXI1, and LCP1 may play a role in EOPE development.
• Splicing changes in FLT4 occur intracellularly, contrasting with extracellular changes in its paralog FLT1 observed in preeclampsia.