S100P promotes trophoblast syncytialization during early placenta development by regulating YAP1

Area of Science:

• Reproductive Biology
• Cell Biology
• Genetics

Background:

• Recurrent pregnancy loss (RPL) is a complex condition often involving placental dysfunction.
• The specific placental changes and molecular regulators underlying RPL require further investigation.
• S100P protein's role in human placental development and RPL is not well understood.

Purpose of the Study:

• To investigate the role of S100P in human placental development.
• To determine the association between S100P expression and recurrent pregnancy loss.
• To elucidate the molecular mechanism by which S100P influences trophoblast syncytialization.

Main Methods:

• Analysis of S100P expression in serum and placental samples from RPL patients.
• Utilizing a human trophoblast stem cell model (ST(2D)-TS^CT) to study S100P function.
• Investigating the impact of S100P on β-hCG secretion and trophoblast syncytialization.
• Examining the interaction between S100P and Yes-associated protein 1 (YAP1) signaling.

Main Results:

• Reduced S100P expression was observed in serum and placental tissues of a subset of RPL patients.
• S100P is specifically expressed in syncytiotrophoblast-like cells (ST(2D)-TS^CT).
• Loss of S100P impaired β-hCG secretion and led to syncytialization failure.
• S100P downregulates YAP1 protein levels, influencing trophoblast stemness and syncytialization.

Conclusions:

• S100P is critical for regulating human trophoblast syncytialization during early placental development through the YAP1 pathway.
• Lower serum S100P levels may serve as a predictive marker for poor pregnancy outcomes.
• S100P evaluation could offer insights into placental biological function in early pregnancy.