Ovarian Fragmentation and AKT Stimulation for Expansion of Fertile Lifespan

Abstract

Since the first baby was born after in vitro fertilization, the female infertility treatment has been well-developed, yielding successful outcomes. However, successful pregnancies for patients with premature ovarian insufficiency and diminished ovarian reserve are still difficult and diverse therapies have been suggested to improve the chances to have their genetically linked offspring. Recent studies demonstrated that the activation Akt pathway by using a phosphatase and tensin homolog enzyme inhibitor and a phosphatidylinositol-3 kinase stimulator can activate dormant primordial follicles in both mice and human ovaries. Subsequent researches suggested that the disruption of Hippo signaling pathway by ovarian fragmentation increased the expression of downstream growth factors and secondary follicle growth. Based on the combination of ovarian fragmentation and Akt stimulation, the in vitro activation (IVA) approach has resulted in successful follicle growth and live births in premature ovarian insufficiency patients. The approach with disruption of Hippo signaling only was also shown to be effective for treating poor ovarian responders with diminishing ovarian reserve, including advanced age women and cancer patients undergoing sterilizing treatments. This review aims to summarize the effectiveness of ovarian fragmentation and Akt stimulation on follicle growth and the potential of IVA in extending female fertile lifespan.

Possibilities of reproductive function realization in patients with premature ovarian insufficiency

“…Фрагментация коры яичника Было обнаружено, что в яичнике млекопитаю щих фрагментация коры яичника на маленькие кубики нарушает сигнальный путь Hippo за счет увеличения полимеризации G-актина в F-актин. Увеличение ядерной транслокации YAP в этом случае стимулирует экспрессию факторов роста (CCN) и ингибиторов апоптоза (BIRC), что в конечном итоге приводит к росту фолликулов [40,41]. В исследование K. Kawamura et al об эффективности метода фрагментации яичников вошли 27 пациенток с ПНЯ в возрасте 37,3 ± 5,8 года и большой продолжительностью аменореи (6,8 ± 2,1 года).…”

Oocyte aging in comparison to stem cells in mice

“…Experiments suggest that as the effects of pressure can be mimicked by stiffness ( Smith et al, 2017 ), age-related ovarian fibrosis increases internal pressure. Intriguingly, there are cases where primordial follicles remain even during POI, and excision of the ovary in vitro can induce follicle activation ( Vo and Kawamura, 2021 ). As intraovarian pressure control has the potential to extend reproductive lifespan, further investigation is required.…”