Biophysical, cellular, and mouse model approaches to investigate the mechanical regulation of folliculogenesis

Folliculogenesis, which is the process by which ovarian follicles develop to support oogenesis and hormone production, is essential for female fertility. Although hormonal and biochemical signaling pathways regulating folliculogenesis have been extensively studied, increasing evidence suggests that mechanical cues within the ovary also play a critical role. The ovary is composed of follicles, corpora lutea, and stroma, each contributing to a biomechanical microenvironment that might change across the reproductive lifespan. Additionally, the spatial organization of the ovary, with a collagen-rich cortex and a softer medulla, may influence follicle activation and growth. This review explores the hypothesis that mechanical properties of the ovary regulate folliculogenesis, integrating current knowledge on ovarian architecture, extracellular matrix composition, and mechanotransduction pathways. We highlight recent findings supporting mechanical regulation of folliculogenesis, discuss contradictory data, and describe the tools and models used to investigate this concept. By considering mechanical forces alongside hormonal and biochemical signals, we propose a more integrated view of the factors governing follicle development, with implications for understanding ovarian physiology and pathology.