Molecular signatures of oocyte viability identified by follicular fluid proteomics

Abstract

Women are born with thousands of ovarian follicles, yet less than 1% will ovulate a mature oocyte. What distinguishes the 99% of follicles destined for demise from the rare 1% that succeed? Here, we leveraged a unique clinical opportunity, paired follicular fluid samples from small antral follicles containing either a viable or an atretic oocyte within the same patients, to uncover the proteomic determinants governing oocyte fate. Our analysis identified nearly 1,500 proteins. Follicular fluid from healthy follicles was enriched with proteins crucial for energy metabolism, antioxidative defense, structural integrity, and robust intercellular signaling networks, supporting oocyte survival and maturation. In contrast, follicular fluid from atretic oocytes exhibited a distinct inflammatory signature characterized by acute-phase and immune activation proteins, indicative of active degeneration. These novel proteomic insights deepen our understanding of human follicle biology and open new avenues for biomarker development, optimization of assisted reproductive technologies, and targeted therapeutic strategies to preserve and enhance female fertility.