Improvement of oocyte quality through the SIRT signaling pathway.

Background: Oocyte quality is one of the major deciding factors in female fertility competence. Methods: PubMed database was searched for reviews by using the following keyword "oocyte quality" AND "Sirtuins". The methodological quality of each literature review was assessed using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement. Main Findings: Oxidative stress has been recognized as the mechanism attenuating oocyte quality. Increasing evidence from animal experiments and clinical studies has confirmed the protective roles of the sirtuin family in improving oocyte quality via an antioxidant effect. Conclusion: The protective roles in the oocyte quality of the sirtuin family have been increasingly recognized.

Effects of Hochuekkito, a traditional Japanese medicine (Kampo), on reproduction of aging female mice.

PURPOSE: To determine the potentials of Hochuekkito (HET) treatment for aging infertility. METHODS: Mice at 36 weeks of age were fed without (control, n = 40) or with low (100 mg/kg/day, n = 24) and high (1000 mg/kg/day, n = 38) doses of HET for 12 weeks. Aging animals at 48 weeks of age were used for in vitro fertilization-embryo transfer (IVF-ET), and their ovaries were subjected to histological and quantitative inflammation analyses. RESULTS: HET administration decreased transcript levels of ovarian inflammatory markers, interleukin 6 (IL-6), IL-1ß, tumor necrosis factor (TNF)-α, and interferon-gamma (IFN-γ) but suppressed ovulation rates and the number of ovulated oocytes in aging mice. Furthermore, HET treatment decreased the rates of oocytes maturation and fertilization and the cumulus-cell expression of TNF-α-induced protein 6 and epidermal growth factor receptor. After IVF-ET, no improvement of declined live offspring rate by aging was achieved by HET administration, although there were no adverse effects on embryo development and implantation as well as gross morphology and bodyweight of pups. CONCLUSION: Present study indicated HET treatment interfered with ovulation and fertilization in aging mice without affecting ovarian follicle development. No improvement on the age-associated decline of live offspring rate and follicle development was achieved after HET treatment.

Female Oncofertility: Current Understandings, Therapeutic Approaches, Controversies, and Future Perspectives.

Recent advances in early detection and oncological therapies have ameliorated the survival rate of young cancer patients. Yet, ovarian impairment induced by chemotherapy and radiotherapy is still a challenging issue. This review, based on clinical and lab-based studies, summarizes the evidence of gonadotoxicity of chemoradiotherapy, the recent approaches, ongoing controversies, and future perspectives of fertility preservation (FP) in female patients who have experienced chemo- or radio-therapy. Existing data indicate that chemotherapeutic agents induce DNA alterations and massive follicle activation via the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Meanwhile, the radiation causes ionizing damage, leading to germ cell loss. In addition to the well-established methods, numerous therapeutic approaches have been suggested, including minimizing the follicle loss in cryopreserved ovarian grafts after transplantation, in vitro activation or in vitro growing of follicles, artificial ovarian development, or fertoprotective adjuvant to prevent ovarian damage from chemotherapy. Some reports have revealed positive outcomes from these therapies, whereas others have demonstrated conflictions. Future perspectives are improving the live birth rate of FP, especially in patients with adverse ovarian reserve, eliminating the risk of malignancy reintroducing, and increasing society's awareness of FP importance.

In Vitro Activation Early Follicles: From the Basic Science to the Clinical Perspectives.

Development of early follicles, especially the activation of primordial follicles, is strictly modulated by a network of signaling pathways. Recent advance in ovarian physiology has been allowed the development of several therapies to improve reproductive outcomes by manipulating early folliculogenesis. Among these, in vitro activation (IVA) has been recently developed to extend the possibility of achieving genetically related offspring for patients with premature ovarian insufficiency and ovarian dysfunction. This method was established based on basic science studies of the intraovarian signaling pathways: the phosphoinositide 3-kinase (PI3K)/Akt and the Hippo signaling pathways. These two pathways were found to play crucial roles in folliculogenesis from the primordial follicle to the early antral follicle. Following the results of rodent experiments, IVA was implemented in clinical practice. There have been multiple recorded live births and ongoing pregnancies. Further investigations are essential to confirm the efficacy and safety of IVA before used widely in clinics. This review aimed to summarize the published literature on IVA and provide future perspectives for its improvement.

Ovarian Fragmentation and AKT Stimulation for Expansion of Fertile Lifespan.

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.