Spatial proteomics and transcriptomics of the maternal-fetal interface in placenta accreta spectrum

Area of Science:

• Reproductive biology
• Immunology
• Genomics

Background:

• Placenta Accreta Spectrum (PAS) is a severe pregnancy complication.
• Placenta increta involves deep trophoblast invasion into the myometrium.
• Understanding the fetal-maternal interface in PAS is crucial.

Purpose of the Study:

• To investigate alterations at the fetal-maternal interface in placenta increta using a systems biology approach.
• To identify molecular mechanisms driving deep trophoblast invasion in PAS.

Main Methods:

• Immunohistochemistry, spatial transcriptomics, and spatial proteomics were employed.
• Analysis of T-cell distribution, transcription factors, gene expression pathways, and protein expression.
• Ligand-receptor interaction analysis was performed.

Main Results:

• Spatial variations in T-cell distribution were observed in placenta increta.
• Upregulation of transcription factors (AP-1, NFKB) and ECM degradation pathways in deep invasion regions.
• Increased trophoblast proliferation, immunosuppressive factors (PD-L1, PD-L2), and fibronectin were noted.
• ITGβ1 ligand interactions, particularly with fibronectin, were central, promoting invasive phenotypes.

Conclusions:

• Deep myometrial invasion in placenta increta is associated with an immunosuppressive environment and excessive trophoblast proliferation.
• Fibronectin-driven AP-1 signaling is implicated in promoting invasive trophoblast phenotypes, potentially secondary to myometrial scarring.