Roles of follicle stimulating hormone and sphingosine 1-phosphate co-administered in the process in mouse ovarian vitrification and transplantation.

Some major challenges of ovarian tissue vitrification and transplantation include follicle apoptosis induced by cryopreservation and ischemia-reperfusion injury, as well as ovarian follicle loss during post-transplantation. This research aimed to investigate the protective effects and underlying mechanisms of follicle-stimulating hormone (FSH) and Sphingosine-1-phosphate (S1P) on vitrified and post-transplantation ovaries. Ovaries from 21-day-old mice were cryopreservation by vitrification with 0.3 IU/mL FSH, 2 µM S1P, and 0.3 IU/mL FSH + 2 µM S1P, respectively, for follicle counting and detection of apoptosis-related indicators. The results demonstrated that FSH and S1P co-intervention during the vitrification process could preserve the primordial follicle pool and inhibit follicular atresia by suppressing cell apoptosis. The thawed ovaries were transplanted under the renal capsule of 6-8 week-old ovariectomized mice and removed 24 h or 7 days after transplantation. The results indicated that FSH and S1P co-intervention can inhibit apoptosis and autophagy in ovaries at 24 h after transplantation, and promote follicle survival by up-regulating Cx37 and Cx43 expression, enhanced angiogenesis in transplanted ovaries by promoting VEGF expression, as well as increased the E2 levels to restore ovarian endocrine function at 7 days after transplantation. The hypoxia and ischemia cell model was established by CoCl2 treatment for hypoxia in human granulosa-like tumor cell line (KGN), as well as serum-free culture system was used for ischemia. The results confirmed that ischemia-hypoxia-induced apoptosis in ovarian granulosa cells was reduced by FSH and S1P co-intervention, and granulosa cell autophagy was inhibited by up-regulating the AKT/mTOR signaling pathway. In summary, co-administration of FSH and S1P can maintain ovarian survival during ovarian vitrification and increase follicle survival and angiogenesis after transplantation.

Correlation between Endometrial Vascular Endothelial Growth Factor Expression and Pregnancy Outcome of Frozen-Thawed Embryo Transfer in Patients with Repeated Implantation Failure.

Objective: Vascular endothelial growth factor (VEGF) is a well-known angiogenic factor that is essential to numerous physiological and pathological processes. VEGF also contributes to embryo implantation by promoting embryo development, enhancing endometrial receptivity (ER), and promoting interactions between the endometrium and developing embryo. Changes in VEGF expression are linked to repeated implantation failure (RIF). Control endometrial tissues demonstrated an increase in VEGF expression during the implant window period, which promoted early villous vascularization and embryo implantation. The purpose of this study is to investigate the relationship between RIF and the expression of ER markers, such as VEGF during the implantation window stage. Methods: The Yinchuan Maternal and Child Health Hospital collected 192 cases of FET endometrial tissues in the implantation window stage between January 2019 and December 2021. Immunohistochemistry was utilized to measure the levels of VEGF expression in patients with RIF (RIF group, n = 82) and patients with a successful pregnancy (control group, n = 110). The relationship between VEGF and the RIF group was analyzed using Spearman's correlation coefficient. Results: VEGF levels were significantly lower during the implantation window stage (P < 0.05). Conclusion: VEGF was expressed in planting window stage. The decrease of VEGF during the implantation window was correlated with RIF.