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

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 th...

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Main Authors: Yubin Li, Yue Hu, Shunye Zhu, Ying Tuo, Bin Cai, Tengfei Long, Wen Zhao, Xiaoxin Ye, XiaoFang Lu, Lingli Long
Format: Article
Language:English
Published: SAGE Publishing 2021-03-01
Series:Cell Transplantation
Online Access:https://doi.org/10.1177/0963689721997151
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spelling doaj-2b8dd1be0ca14a02904744f23608b5632021-03-30T22:34:24ZengSAGE PublishingCell Transplantation1555-38922021-03-013010.1177/0963689721997151Protective Effects of Reduced Glutathione and Ulinastatin on Xeno-transplanted Human Ovarian Tissue Against Ischemia and Reperfusion InjuryYubin Li0Yue Hu1Shunye Zhu2Ying Tuo3Bin Cai4Tengfei Long5Wen Zhao6Xiaoxin Ye7XiaoFang Lu8Lingli Long9 These authors contributed equally to this work. These authors contributed equally to this work. Department of Pediatrics, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China The Reproductive Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Department of Gynecology and Obstetrics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guanghzou, China The Reproductive Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China University of New South Wales, Sydney, High St. Kensington, New South Wales, Australia These authors contributed equally to this work. These authors contributed equally to this work.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.https://doi.org/10.1177/0963689721997151
collection DOAJ
language English
format Article
sources DOAJ
author Yubin Li
Yue Hu
Shunye Zhu
Ying Tuo
Bin Cai
Tengfei Long
Wen Zhao
Xiaoxin Ye
XiaoFang Lu
Lingli Long
spellingShingle Yubin Li
Yue Hu
Shunye Zhu
Ying Tuo
Bin Cai
Tengfei Long
Wen Zhao
Xiaoxin Ye
XiaoFang Lu
Lingli Long
Protective Effects of Reduced Glutathione and Ulinastatin on Xeno-transplanted Human Ovarian Tissue Against Ischemia and Reperfusion Injury
Cell Transplantation
author_facet Yubin Li
Yue Hu
Shunye Zhu
Ying Tuo
Bin Cai
Tengfei Long
Wen Zhao
Xiaoxin Ye
XiaoFang Lu
Lingli Long
author_sort Yubin Li
title Protective Effects of Reduced Glutathione and Ulinastatin on Xeno-transplanted Human Ovarian Tissue Against Ischemia and Reperfusion Injury
title_short Protective Effects of Reduced Glutathione and Ulinastatin on Xeno-transplanted Human Ovarian Tissue Against Ischemia and Reperfusion Injury
title_full Protective Effects of Reduced Glutathione and Ulinastatin on Xeno-transplanted Human Ovarian Tissue Against Ischemia and Reperfusion Injury
title_fullStr Protective Effects of Reduced Glutathione and Ulinastatin on Xeno-transplanted Human Ovarian Tissue Against Ischemia and Reperfusion Injury
title_full_unstemmed Protective Effects of Reduced Glutathione and Ulinastatin on Xeno-transplanted Human Ovarian Tissue Against Ischemia and Reperfusion Injury
title_sort protective effects of reduced glutathione and ulinastatin on xeno-transplanted human ovarian tissue against ischemia and reperfusion injury
publisher SAGE Publishing
series Cell Transplantation
issn 1555-3892
publishDate 2021-03-01
description 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.
url https://doi.org/10.1177/0963689721997151
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