Ovarian Matrisome Dynamics and αvβ3‐Mediated Regulation in Early Follicular Development

ABSTRACT Early follicular development (EFD) spans the growth from primordial to small antral stages and is crucial for maintaining ovarian function. However, the specific role of matrisome during this process remains largely undefined. We perform integrated transcriptomic and proteomic analyses of prepubertal mouse ovaries to delineate the dynamics of the matrisome during EFD. Cross‐species comparison reveals a significant enrichment of matrisome‐associated items in mice, sheep, and pigs. We employ instrumental nanoindentation and Raman spectroscopy to obtain mechanical, topographical, and biochemical spectral data. And integrin αvβ3 is identified as a critical receptor mediating matrisome signals to follicles. Functional inhibition of αvβ3 exhibits a dual effect: it promotes primordial follicle activation, yet concurrently induces follicular atresia. Moreover, disruption of matrisome signals hinders secondary follicles growth by attenuating the cytoskeletal integrity and viability of granulosa cells; it also compromises oocyte maturation by disturbing the meiosis progression and mitochondrial function. Importantly, the role of matrisome is underscored in human ovarian tissues, which exhibited similar collagen remodeling and stage‐specific αvβ3 expression. Collectively, our work constructs a multi‐dimensional atlas of matrisome during EFD and determines αvβ3 as a pivotal mediator of matrisome‐follicle crosstalk, offering mechanistic insights into ovarian dysfunction and impaired follicular development.