iTRAQ-based quantitative proteomics reveals dysregulation of fibronectin 1 contributes to impaired endometrial decidualization in recurrent implantation failure

Abstract

Recurrent implantation failure (RIF) poses challenges to successful embryo implantation. In this study, we utilized isobaric tags for relative and absolute quantification (iTRAQ) to profile endometrial protein abundance in RIF patients. Through functional and pathway analyses, ECM-related proteins including fibronectin 1 (FN1), collagen type I alpha 2 chain (COL1A2), and integrin beta-1 (ITGB1) were revealed to be associated with RIF. Correlation analysis identified TGF-β1 as an upstream regulator of FN1. Knockdown experiments showed TGF-β1 downregulation could inhibit FN1 expression to inhibit decidualization markers. Our findings suggest a mechanistic link between TGF-β1/FN1 axis dysregulation and impaired decidualization observed in RIF.

Significance

Our study addresses the pressing issue of RIF, a significant obstacle in assisted reproductive technology. By employing isobaric tags for relative and absolute quantification (iTRAQ), we comprehensively analyzed endometrial protein abundance in RIF patients. Through functional and pathway enrichment analyses, we identified dysregulation in extracellular matrix (ECM)-related proteins, including FN1, COL1A2, and ITGB1, shedding light on their potential roles in implantation failure. Additionally, our correlation analysis revealed TGF-β1 as an upstream regulator of FN1, suggesting a novel regulatory axis involved in decidualization. Knockdown experiments further demonstrated the impact of TGF-β1 and FN1 on decidualization markers. This study contributes to a better understanding of the molecular mechanisms underlying RIF.