Surface mechanics and compressive stress impact mammalian follicle development

The maturation of functional eggs in ovaries is essential for successful reproduction in mammals. Despite its biological and clinical importance, the underlying mechanisms regulating folliculogenesis remain enigmatic. Here, using murine ovaries, we report that the theca cells surrounding secondary follicles play a critical role in regulating follicle development through mechanical signalling. Using biophysical approaches, we found that the contractile theca cells exert significant compressive stress to the follicular interior through active assembly of fibronectin. Manipulation of compressive stress by targeting theca cell contractility, basement membrane integrity or intrafollicular pressure leads to changes in follicle size and mechanics, granulosa cell YAP signalling and oocyte-granulosa cell communications. Transcriptomics and quantitative immunofluorescence reveal that compressive stress impacts functional follicle growth through regulating the balance between granulosa cell proliferation and death that drives tissue pressure homeostasis. Altogether, our study uncovers unique mechanical functions of theca cells and provides quantitative evidence of the role of compressive stress in regulating mammalian folliculogenesis.