| Popis: |
Female ovary is the earliest degenerated organ and it faces distinct medical disadvantages that impair primordial follicle reserve and oocyte quality. Herein, we found that bridge integrator 2 (Bin2) was predominant within mouse ovaries and oocytes, and global-knockout of Bin2 improved both female fertility and oocyte quality with healthy physiology in mice. Ovarian quantitative proteomics and phosphomics showed that Bin2 knockout specifically decreased only p-RPS6 of mTOR pathway; meanwhile, it increased nicotinamide nucleotide transhydrogenase (NNT), the free-radical detoxifier, over 6-fold. Mechanically, phosphorylation at Thr423 & Ser424 translocated membrane Bin2 into cytoplasm to phosphorylate RPS6, while p-RPS6 bound 42-95 bp NNT UTR to inhibit NNT translation. We then synthesized a peptide (BPP) to mimic Bin2 inhibition, and found that 3-week BPP injection improved primordial follicle reserve and oocyte quality in aging or chemotherapeutics-treated mice. In all, Bin2 inhibition improve both primordial follicle reserve and oocyte quality without discernible side effects. |
