Membrane-bound peptidases regulate human extravillous trophoblast invasion

Area of Science:

• Reproductive biology
• Cell biology
• Human placentation

Background:

• Extravillous trophoblast (EVT) invasion is crucial for human placentation but its regulation is unclear.
• Mechanisms controlling EVT invasion into maternal arteries and decidua require further characterization.

Purpose of the Study:

• To investigate the role of membrane-bound peptidases and chemokine systems in regulating EVT invasion during human placentation.
• To identify specific peptidases and chemokines involved in controlling EVT migration and invasion.

Main Methods:

• Detection of cell surface peptidases (dipeptidyl peptidase IV, carboxypeptidase-M, laeverin) and chemokine receptors (CCR-1) on EVT.
• Inhibition of peptidases to assess effects on JEG-3 cell invasion.
• Isolation and culture of primary EVT for invasion assays.
• Analysis of platelet interactions with EVT.

Main Results:

• Dipeptidyl peptidase IV and carboxypeptidase-M were expressed on EVT, and their inhibition enhanced JEG-3 cell invasion.
• CCR-1 was specifically expressed on EVT migrating towards maternal arteries, and RANTES enhanced EVT invasion.
• Platelets, found among endovascular trophoblast, enhanced cultured EVT invasion.
• Laeverin was specifically expressed on EVT in deep decidua.

Conclusions:

• Membrane-bound peptidases and the chemokine RANTES system cooperate to regulate EVT invasion during early human placentation.
• These molecular players, including platelets, likely control the extent and depth of EVT invasion within the maternal uterine environment.