The intrinsic impact of mechanical stress on the maintenance of oocyte dormancy

In the mammalian ovary, most oocytes remain dormant, and their dormant status plays a central role in maintaining the reservoir population of the female germ line. The equilibrium between the dormant and active states, the latter of which is responsible for producing mature oocytes, is therefore crucial for ensuring the sustained reproductive capability of females. We have previously reported that mechanical stress in the ovary plays a crucial role in oocyte dormancy. However, the mechanism underlying this relation remains unclear. Here we demonstrated that the mechanical stress is directly transduced into the oocytes, rather than to surrounding granulosa cells. Culture experiments and live-imaging analysis revealed the nuclear localization of FOXO3, a hallmark of oocyte dormancy, within oocytes cultured alone in response to mechanical stress. Interestingly, we discovered that the cytological response to mechanical stress was accompanied by ligand-independent internalization of the c-kit receptor, which dampens intracellular signaling and prevents oocyte activation. These results shed light on the relation between mechanical stress and oocyte dormancy and provide clues toward a greater understanding of female reproductive capability. Overall design: After culturing female mouse embryonic ovary under an external pressure (33.3 kPa), Stella-CFP- positive cells were isolated by fluorescence-activated cell sorting (FACS) and analyzed using RNA sequencing (RNA-seq). *************************************************************** The table below lists GEO accessions reused/reanalyzed for this study. ***************************************************************