Dynamic maternal and fetal Notch activity and expression in placentation

Area of Science:

• Reproductive biology
• Developmental biology
• Cell signaling

Background:

• Murine placentation depends on trophoblast Notch2.
• Jagged1, a Notch ligand, is reduced in preeclampsia trophoblasts.
• Placental cell expression of Notch proteins and ligands requires definition.

Purpose of the Study:

• Identify placental cell subtypes with active Notch signaling.
• Characterize Notch protein and ligand expression in the decidua and placenta.
• Correlate Notch signaling activity with specific cell types.

Main Methods:

• Utilized Notch reporter transgenic mice for canonical Notch activity.
• Employed immunofluorescence staining to analyze Notch1, 2, 3, 4, Delta-like 4 (Dll4), and Jagged1 (Jag1) expression.
• Examined expression during early and mature placentation.

Main Results:

• Notch signaling is active in maternal/fetal endothelial cells and trophoblasts throughout placentation.
• Dll4, Jag1, Notch1, and Notch4 are present in maternal decidual vasculature.
• Dll4, Jag1, Notch1, Notch2, and Notch4 show varied expression in fetal vasculature, trophoblast subtypes, and giant cells.

Conclusions:

• Canonical Notch activity and distinct expression patterns of Notch proteins/ligands are evident in placental endothelium and trophoblasts.
• Notch1, Notch2, Notch4, Dll4, and Jag1 likely have overlapping and distinct roles in placentation.
• Further study of Notch signaling defects in preeclampsia mouse models could illuminate disease mechanisms.