2026-01-13 山梨大学,科学技術振興機構
<関連情報>
- https://www.jst.go.jp/pr/announce/20260113/index.html
- https://www.jst.go.jp/pr/announce/20260113/pdf/20260113.pdf
- https://www.pnas.org/doi/10.1073/pnas.2526249123
機械的ストレスが卵母細胞休眠の維持に及ぼす本質的な影響 The intrinsic impact of mechanical stress on the maintenance of oocyte dormancy
Go Nagamatsu, Kenjiro Shirane, Yuzuru Kato, +4 , and Katsuhiko Hayashi
Proceedings of the National Academy of Sciences Published:January 16, 2026
DOI:https://doi.org/10.1073/pnas.2526249123
Significance
Oocyte dormancy is a key state that ensures sustained female reproductive capacity, yet the mechanisms maintaining this state in the ovary remain elusive. Our findings reveal that mechanical stress has a direct impact on the induction of oocyte dormancy by promoting ligand-independent internalization of the c-kit receptor, which desensitizes KIT-mediated signaling required for follicular activation. This process, in turn, induces nuclear localization of FOXO3, a transcription factor that serves as a gatekeeper of oocyte dormancy. Together, our study uncovers a mechanism that safeguards the reservoir of dormant oocytes and provides insight into the long-term maintenance of the ovarian reserve.
Abstract
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 the 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 found 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.
