Ovarian Mechanobiology: Understanding the Interplay Between Mechanics and Follicular Development

The ovary is a dynamic organ where mechanical forces profoundly regulate follicular development, oocyte maturation, and overall reproductive function. These forces, originating from the extracellular matrix (ECM), granulosa and theca cells, and ovarian stroma, influence cellular behavior through mechanotransduction, translating mechanical stimuli into biochemical responses. This review explores the intricate interplay between mechanical cues and ovarian biology, focusing on key mechanosensitive pathways such as Hippo signaling, the PI3K/AKT pathway, and cytoskeletal remodeling, which govern follicular dormancy, activation, and growth. Additionally, it examines how ovarian aging disrupts the mechanical microenvironment, with ECM stiffening and altered mechanotransduction contributing to a decline in ovarian reserve and reproductive potential. Emerging technologies, including 3D culture systems and organ-on-chip platforms, are highlighted for their ability to replicate the ovarian microenvironment and advance drug discovery and therapeutic interventions. By integrating mechanobiological principles, this review aims to enhance our understanding of ovarian function and provide new strategies for preserving fertility and combating infertility.