SAA1 regulates pro-labour mediators in term labour by activating YAP pathway

Area of Science:

• Reproductive biology
• Molecular endocrinology
• Immunology

Background:

• Term labor involves inflammation, myometrial contractility, and cervical ripening.
• The role of Serum amyloid A1 (SAA1), an acute-phase protein, in human labor is unknown.
• Understanding SAA1's regulatory mechanisms is crucial for labor onset research.

Purpose of the Study:

• Investigate the role and regulatory mechanisms of SAA1 in human term labor.
• Determine if SAA1 influences inflammatory responses and contraction-associated factors.
• Elucidate the molecular pathways, specifically the YAP pathway, involved in SAA1's function during labor.

Main Methods:

• Quantified SAA1 mRNA and protein expression in human myometrial tissues from laboring and non-laboring women.
• Assessed SAA1 expression in primary myometrial cells stimulated with IL-1β and TNF-α.
• Utilized siRNA to knockdown SAA1 and analyzed the impact on inflammatory mediators and contraction-associated factors.
• Investigated the involvement of the YAP pathway by examining phosphorylated YAP (pYAP) levels and the effects of YAP overexpression.

Main Results:

• SAA1 expression was significantly increased in term laboring myometrial tissues compared to non-laboring tissues.
• Pro-inflammatory cytokines (IL-1β, TNF-α) upregulated SAA1 expression in primary myometrial cells.
• SAA1 knockdown reduced the expression and secretion of pro-inflammatory cytokines, chemokines, adhesion molecules, and contraction-associated factors.
• SAA1's effects were mediated by the YAP pathway, with SAA1 knockdown decreasing pYAP and YAP overexpression reversing SAA1's effects.

Conclusions:

• SAA1 expression is elevated during human term labor.
• SAA1 accelerates the inflammatory response associated with parturition by activating the YAP pathway.
• This study provides a novel understanding of the molecular mechanisms underlying labor onset.