Improvement in the quality of heterotopic allotransplanted mouse ovarian tissues with basic fibroblast growth factor and fibrin hydrogel
Improvement in the quality of heterotopic allotransplanted mouse ovarian tissues with basic fibroblast growth factor and fibrin hydrogel
复制标题
使用碱性成纤维细胞生长因子和纤维蛋白水凝胶改善异位同种异体移植小鼠卵巢组织的质量。
DOI：
10.1093/humrep/det296
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发表时间：
2013-10-01
影响因子：
6.1
通讯作者：
Qiao, Jie
中科院分区：
文献类型：
--
作者：
Gao, Jiang-Man;Yan, Jie;Qiao, Jie
碱性成纤维细胞生长因子（bFGF）与纤维蛋白水凝胶联合应用能否促进小鼠卵巢组织异位移植后卵泡发育和血管重建？用较高浓度处理移植的卵巢组织（75、100和150 μ g/ml），但不低于此浓度（25和50 μ g/ml）的bFGF显著改善原始卵泡存活和血管生成，移植卵巢组织保存女性生育能力受到大量卵泡丢失和缺血的限制，由于预期的血运重建延迟而导致的再灌注损伤。将18天大的ICR小鼠的卵巢组织包裹在混合有不同浓度的bFGF的盐水水凝胶中，然后移植到成年雌性小鼠的皮肤下1周。将未经纤维蛋白水凝胶和bFGF处理的卵巢组织指定为对照组I，将经纤维蛋白水凝胶但未经bFGF处理的卵巢组织指定为对照组II。将25和50 μ g/ml bFGF处理的卵巢组织设为低浓度组，75、100和150 μ g/ml bFGF处理的卵巢组织设为高浓度组，通过组织学分析评价卵泡数量和卵泡分类。用增殖细胞核抗原免疫染色证实卵泡增殖，用抗活性caspase-3染色证实细胞凋亡。移植后1周取卵巢组织，用CD31抗体染色新生血管上皮细胞，免疫组化法检测新生血管密度。与对照组相比，高浓度bFGF处理的移植卵巢组织中，卵泡的存活和增殖明显增加，卵泡和基质细胞的凋亡明显减少，血管生成明显增强。用较低浓度的bFGF治疗并没有改善卵泡存活和血液重建。由于小鼠和人类之间的生理差异，所获得的结果可能无法完全外推到人类。本研究探讨了bFGF在移植卵巢组织中的作用，证实bFGF可通过增加卵泡数量，促进卵泡发育，新血管生成本研究为卵巢组织移植在临床上的进一步研究和应用奠定了基础，最终可能使女性受益于生育保护。这项工作得到了中国科学技术部赠款的部分支持（973计划; 2011 CB 944503 to Q.J.），国家教育部长江学者和高校创新研究团队项目（30825038 to Q.J.），国家自然科学基金青年学者项目（81200470，Y.J.; 81000275，Y.L.Y.）。所有作者均无任何利益冲突。
Does basic fibroblast growth factor (bFGF) in combination with fibrin hydrogel improve follicle development and revascularization of heterotopically transplanted mouse ovarian tissues?Treatment of transplanted ovarian tissues with higher concentrations (75, 100 and 150 g/ml), but not lower concentrations (25 and 50 g/ml), of bFGF significantly improved primordial follicle survival and angiogenesis, while apoptosis of follicles and stromal cells was significantly decreased.Use of transplanted ovarian tissues in female fertility preservation is limited by the massive loss of follicles and ischemia-reperfusion injury due to the expected delay in revascularization.Ovarian tissues from 18-day-old ICR mice were encapsulated in brin hydrogel mixed with different concentrations of bFGF, then transplanted under the skin of adult female mice for 1 week. The ovarian tissues treated without fibrin hydrogels and bFGF were designated as Control group I, and the ovarian tissues treated with fibrin hydrogels but without bFGF were designated as Control group II. The ovarian tissues treated with 25 and 50 g/ml bFGF were designated as the lower concentration group, and the ovarian tissues treated with 75, 100 and 150 g/ml bFGF were designated as the higher concentration group.Assessment of follicular quantity and follicle classification was carried out by histologic analysis. Follicle proliferation was evidenced by immunostaining with proliferating cell nuclear antigen and apoptosis was verified by anti-active caspase-3 staining. Epithelial cells of new blood vessels were stained using CD31 antibody to evaluate neoangiogenesis, and the blood vessel density was analyzed by immunohistochemistry.The ovarian tissues were recovered 1 week post-transplantation. Compared with the control group, the survival and proliferation of the follicles was significantly increased, the apoptosis of follicles and stromal cells was significantly decreased, and angiogenesis was significantly enhanced when the transplanted ovarian tissues were treated with a higher concentration of bFGF. Treatment with a lower concentration of bFGF did not improve follicle survival and blood revascularization.The results obtained may not be fully extrapolated to humans because of the physiologic differences between mice and humans.For the first time, the present study investigated the role of bFGF in transplanted ovarian tissues and demonstrated that bFGF might significantly improve the quality of transplanted ovarian tissues by increasing follicle quantity and promoting neoangiogenesis. This study sets the stage for further study and application of ovarian tissue transplantation in clinics, and may eventually benefit females for fertility preservation.This work was partially supported by the Ministry of Science and Technology of China Grants (973 Program; 2011CB944503 to Q.J.), the Program for Changjiang Scholars and Innovative Research Team in University of Ministry of Education of China (30825038 to Q.J.), and the National Natural Science Funds for Young Scholar (81200470 to Y.J. and 81000275 to Y.L.Y.). None of the authors have any conflicts of interest.