YY1/ITGA3 pathway may affect trophoblastic cells migration and invasion ability

Area of Science:

• Reproductive biology
• Molecular genetics
• Cell biology

Background:

• Recurrent spontaneous abortion (RSA) affects ~2.5% of women, with unclear pathogenesis.
• Transcription factor Yin-Yang 1 (YY1) influences trophoblast invasion, a key factor in RSA.
• Understanding YY1's specific molecular mechanisms in trophoblast cells is critical.

Purpose of the Study:

• To elucidate the molecular mechanism of YY1 in trophoblast cells.
• To investigate the role of YY1 in regulating gene expression related to trophoblast function.
• To determine the impact of YY1 and its target genes on trophoblast invasion and cytoskeleton formation.

Main Methods:

• RNA sequencing (RNA-seq) and Chromatin immunoprecipitation sequencing (Chip-seq) to identify YY1-regulated genes.
• Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.
• Experimental validation including RT-PCR, Western blot, Immunofluorescence, and Dual-luciferase reporter gene assay.

Main Results:

• YY1 knockdown significantly altered gene expression in HTR-8/SVneo cells.
• Pathway analysis suggested a role for Integrins in trophoblast biological functions.
• YY1 directly regulates ITGA3 expression by binding to its promoter, affecting ITGA3 mRNA and protein levels.
• YY1 and ITGA3 influence focal adhesion kinase phosphorylation and cytoskeleton formation.
• YY1's effect on ITGA7 was not significant.

Conclusions:

• YY1 plays a critical role in trophoblast invasion ability.
• YY1 regulates trophoblast invasion primarily through ITGA3.
• The YY1/ITGA3 pathway impacts trophoblast invasion by modulating cytoskeleton formation, offering potential insights into RSA pathogenesis.