Protective Effects of Reduced Glutathione and Ulinastatin on Xeno-transplanted Human Ovarian Tissue Against Ischemia and Reperfusion Injury

Abstract

Recently, transplantation of cryopreserved ovarian tissue is the method for fertility preservation for oncologic and nononcologic reasons. The main challenge of ovarian cryopreservation followed by transplantation is that ischemia reperfusion injury (IRI) induced the loss of follicles. The aim of this study was to evaluate the effects of glutathione (GSH), ulinastatin (UTI) or both (GSH+UTI) on preventing ischemia reperfusion-induced follicles depletion in ovarian grafts. Ovarian fragments were collected from 20 women aged 29±6 years. Frozen-thawed human ovarian tissue was xenografted into SCID mice, at the same time GSH, UTI and GSH+UTI was administrated respectively. The ovarian grafts were collected at the 1st, 3rd, 7th, 14th, 28th, 56th, and 85th day after xenotransplantation. Follicle survival rate was measured by H&E staining and Live/Dead staining. Angiogenic activity and macrophage recruitment was evidenced by immunohistochemical staining. The oxidative stress and inflammatory cytokines in human ovarian xenografts were measured by real-time PCR. The results indicated that after the treatments of GSH, UTI and GSH+UTI in the hosts, follicular survival in ovarian grafts were improved. The level of VEGF, CD31, and antioxidant enzymes superoxide dismutase 1 and superoxide dismutase 2 in ovarian grafts were increased. Accumulation of macrophages, level of IL6 and TNF-α, as well as malondialdehyde was decreased in ovarian grafts from treated groups. In conclusion, administration of GSH, UTI and GSH+UTI decreased the depletion of follicles in human grafts post-transplantation by inhibiting IRI-induced antiangiogenesis, oxidative stress and inflammation.

Genetic Basis of Follicle Development in Dazu Black Goat by Whole-Transcriptome Sequencing

“…Considerable attention has been paid to the pathways involved in the regulation of ovarian function, such as corpus luteum formation and steroid production [ 37 , 38 , 39 ]. In this study, numerous DEmRNAs were enriched in Wnt [ 40 ], MAPK [ 41 ], TGF-β [ 42 ], PI3K-Akt [ 43 ], Hippo [ 44 ], and glutathione metabolic [ 45 ] signaling pathways, which have been verified to be associated with FD. Such pathways could improve the treatment of infertility with reduced ovarian reserve in the future [ 43 , 46 , 47 , 48 ].…”

The Effects of Dexmedetomidine on Abdominal Aortic Occlusion-Induced Ovarian Injury via Oxidative Stress and Apoptosis

“…A decrease in levels of GSH, an antioxidant enzyme, was observed following I/R injury in the present study. GSH suppresses I/R injury and plays a very important role in the cellular defense system [Li et al, 2021]. Therefore, the depletion of GSH indicates the response to damage caused by free radicals.…”

Ulinastatin affects focal cerebral ischemia–reperfusion injury via SOCS1‐mediated JAK2/STAT3 signalling pathway

“…Previously, Yano et al 19 proved that 300 000 U/kg intravenous preconditioning of UTI was neuroprotective by evaluating infarct size, neutrophil infiltration, and nitro‐tyrosine deposition in the ischemic hemisphere. More recently, administration of UTI has been found to decrease the depletion of follicles in human grafts post‐transplantation by repressing IRI‐induced anti‐angiogenesis, oxidative stress and inflammation, 20 indicating the possible anti‐inflammatory effects of UTI. UTI could protect the brain against IRI as well, which may be related to the alleviation of inflammation reaction in the early stage 21 .…”