Optimal FSH usage in revascularization of allotransplanted ovarian tissue in mice

Abstract

BackgroudOvarian transplantation is a useful method for preserving the fertility of young women with cancer who undergo radiotherapy and chemotherapy. Follicle-stimulating hormone (FSH) is use to protect transplanted ovarian tissues from ischemia injury through promoting revascularization after transplantation, but the side effect of high level FSH is ovarian overstimulation leading to substantial follicular loss. In this study, we investigated the optimal usage of FSH on revascularization in the in vitro cultured ovarian tissues before and after transplantation.ResultsFSH mainly exhibited an additive response in the gene and protein expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and follicle stimulating hormone receptor (FSHR) with its raised concentrations (0.15 IU/ml, 0.30 IU/ml and 0.60 IU/ml) and prolonged treatment (3 h, 6 h, 12 h, 24 h). The concentrations with 0.60 IU/ml FSH could obviously promoted the expression of VEGF, bFGF and FSHR, but under this concentration FSH could also overstimulated the ovarian tissue leading to follicular loss. With the increase of culture time, the gene and protein expression of VEGF and bFGF both were up-regulated in all of the FSH added groups, but FSHR expression decreased when culture time exceeded 12 h. So we chose 0.30 IU/ml FSH added concentration and 6 h culture time as the FSH usage condition in functional revascularization verification experiment, and found that under this condition FSH promoted 2.5 times increase of vascular density in treated group than in control group after ovarian tissues transplantation.ConclusionOvarian intervention with 0.30 IU/ml FSH for 6 h is an optimal FSH usage condition which could accelerate the revascularization in the allotransplanted ovarian tissue and can not produce ovarian overstimulation.

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

“…Freezing damage during ovarian vitrification, follicle losses due to ischemia and hypoxia during the initial stage of avascular anastomosis transplantation and egg development damage due to delayed angiogenesis are the “bottlenecks” that limit the general application of this technology [ 12 ]. FSH is an important hormone in follicle growth and development, and has been shown to reduce follicle loss during ovarian vitrification and transplantation, and increase angiogenesis [ 28 , 29 , 34 ]. S1P is used as an anti-apoptotic agent in ovarian vitrification and transplantation [ 35 ]; however, due to its short half-life, the protective effect cannot be produced continuously [ 36 ].…”

“…After one week of cryopreservation, the ovaries were thawed for 10 min with a gradient thawing solution and postcultured in culture solution for 2 h at 37℃ with 5% CO 2 . The ovary transplantation procedures were performed according to previously described [ 28 ]. The dorsolateral skin of recipient mice was shaved and sterilized after anesthesia, and then the bilateral ovaries were removed through small dorsolateral skin incisions, and the kidneys were identified on both sides of the spine and fixed.…”

“…Studies have indicated that FSH can promote S1P production in ovarian granulosa cells [ 27 ]. Our previous research showed that FSH can enhance the blood supply of transplanted ovaries, improve the survival rate of follicles, and inhibit ovarian cell apoptosis [ 28 , 29 ]. Since S1P cannot sustain its effects in vitro, we believe that co-administration of S1P and appropriate concentration of FSH stimulate endogenous S1P production and prolong its biological activity.…”

Follicular development and the expression of BAX and vascular endothelial growth factor in transplanted ovaries in uni- and bilateral ovariectomized mice: An experimental study

“…In unilaterally ovariectomized mice, the remaining ovary could produce enough estradiol and inhibition to sustain negative feedback on the hypothalamus-pituitary ovary axis, resulting in lower FSH level, compared to bilaterally ovariectomized group (27). While in the latter group, an immediate lack of negative feedback after grafting could facilitate the production of gonadotropin, which releases GnRH, FSH, and LH hormones leading to improved revascularization and growth of follicles in grafted ovaries (15,(27)(28)(29).…”

Intravoxel Incoherent Motion and Dynamic Contrast-Enhanced Magnetic Resonance Imaging Can Differentiate Between Atypical Cartilaginous Tumors and High-Grade Chondrosarcoma: Correlation With Histological Vessel Characteristics

“…8 Hypoxia can upregulate hypoxia-inducible factor-1α (HIF-1α) expression and increase the secretion of vascular endothelial growth factor (VEGF), which plays an important role in promoting angiogenesis and proliferation in many pathological conditions. 9,10 Moreover, CD34 is an endothelial antigen that is used to illustrate microvessel density (MVD) as a measure of the degree of neoangiogenic activity. A high MVD was associated with poor prognosis in chondrosarcoma, and predicted histological grade.…”