Fibroblast Activation Protein (FAP) as a Serum Biomarker for Fibrotic Ovarian Aging: A Clinical Validation Study...

Area of Science:

• Reproductive biology
• Biomarker discovery
• Ovarian aging research

Background:

• Chronological age is an insufficient indicator of reproductive capacity.
• Ovarian aging involves fibrotic remodeling of the ovarian stroma, currently unassessable by clinical tools.

Purpose of the Study:

• To identify and validate a novel serum biomarker for fibrotic ovarian aging.
• To apply machine learning to human ovarian transcriptomic data for biomarker identification.

Main Methods:

• Supervised machine learning applied to GTEx transcriptomic data to identify candidate genes.
• Clinical validation of fibroblast activation protein (FAP) and collectin-11 (COLEC11) in patient cohorts.
• Analysis of serum FAP/COLEC11 levels against ovarian reserve markers (e.g., AMH) and hormonal indices.

Main Results:

• Serum FAP levels inversely correlated with anti-Müllerian hormone (AMH) (r = -0.61, p = 0.001), particularly in women with diminished ovarian reserve (DOR).
• FAP levels were independent of age and central hormonal regulation, indicating stromal specificity.
• COLEC11 correlated with age but did not differentiate DOR status.

Conclusions:

• Circulating FAP is a valid biomarker for age-independent, fibrotic ovarian aging.
• FAP provides stromal-specific information not captured by conventional hormonal markers.
• FAP holds potential for improved reproductive risk assessment and understanding ovarian aging pathophysiology.