Proceedings of the National Academy of Sciences · 2013 · 892 citations · 27 references
MedicineEndocrinologyGynecologyEmbryo TransferIn Vitro FertilizationInfertilityFemale InfertilityFollicular DynamicsOocyte RetrievalOogenesisOvarian FunctionOvarian PhysiologyFollicle Growth PatternsFollicular Development RegulationFollicular SignalingMenopausal StatusOocyte In Vitro FertilizationOvarian Follicle ActivationOvarian Insufficiency ManagementOvulatory Mechanisms
Human ovaries contain follicles that release eggs upon maturation, but primary ovarian insufficiency causes early menopause with few follicles, leaving egg donation as the sole fertility option. The study used in‑vitro activation by ovarian fragmentation to disrupt Hippo signaling and pharmacologic Akt stimulation on removed ovarian tissue. They showed Hippo and Akt pathways control follicle growth, and after grafting treated tissue back, rapid follicle development yielded mature eggs and a live birth following IVF. Kawamura et al.
Significance Human ovaries hold follicles containing oocytes. When follicles mature, they release eggs for fertilization. Patients with primary ovarian insufficiency develop menopausal symptoms at less than 40 y of age. They have few remaining follicles and their only chance for bearing a baby is through egg donation. Kawamura et al. demonstrated that Hippo and Akt signaling pathways regulate follicle growth. Using an in vitro activation approach, they first removed ovaries from infertile patients, followed by fragmentation to disrupt Hippo signaling and drug treatment to stimulate Akt signaling. After grafting ovarian tissues back to patients, they found rapid follicle growth in some patients and successfully retrieved mature eggs. After in vitro fertilization and embryo transfer, a live birth is now reported.
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