Epigenetic changes regulating the epithelial-mesenchymal transition in human trophoblast differentiation

Area of Science:

• Reproductive Biology
• Developmental Biology
• Epigenetics

Background:

• Human placental extravillous trophoblast (EVT) differentiation involves changes in proliferative and invasive capacity.
• Abnormal EVT invasion is linked to preeclampsia and placenta accreta spectrum disorders.
• Understanding normal EVT differentiation is crucial for addressing placental pathologies.

Purpose of the Study:

• To characterize the gene expression and DNA methylation changes during human cytotrophoblast (CTB) to EVT differentiation.
• To identify trophoblast-specific epithelial-mesenchymal transition (EMT) signatures.
• To investigate the functional role of epigenetically regulated genes in EVT invasion.

Main Methods:

• Purified human CTB and EVT cell gene expression analysis.
• Genome-wide DNA methylation profiling.
• Functional studies using JEG3 trophoblast cells and RUNX1 manipulation.

Main Results:

• CTB to EVT differentiation involves a trophoblast-specific EMT.
• EVT cells exhibit genome-wide hypomethylation with locus-specific gains of methylation (GOM).
• RUNX1, a key EMT gene, shows GOM and is functionally important for trophoblast migration and invasion.

Conclusions:

• Epigenetic regulation, particularly locus-specific GOM, plays a significant role in EVT differentiation and invasion.
• EMT pathways and genes like RUNX1 are critical for normal EVT function.
• Dysregulation of these epigenetically controlled processes has implications for obstetric disorders.