Shen Jian, Cao Dai, Sun Jing-Li
Department of Obstetrics and Gynecology, General Hospital of Northern Theater Command (Heping Campus), Shenyang 110000, Liaoning Province, China.
World J Stem Cells. 2020 Apr 26;12(4):277-287. doi: 10.4252/wjsc.v12.i4.277.
Premature ovarian insufficiency (POI) and premature ovarian failure (POF) have become one of the major problems threatening women of childbearing age. Studies have shown that stem cells transplanted from bone marrow, umbilical cord, peripheral blood and amniotic fluid can migrate and proliferate to the ovary, promote ovarian function repair, increase the number of follicles and granulosa cells at all levels of ovary, improve endocrine function, and can differentiate into oocytes in specific ovarian environment to restore fertility to some extent.
To study the ability of human umbilical cord mesenchymal stem cells (hUCMSCs) to repair ovarian injury after chemotherapy.
A total of 110 female BALB/c mice (aged 7-8 wk old) with body masses of 16.0-20.0 g were selected. The mice were fed until 12 wk of age, and cyclophosphamide was administered by intraperitoneal injection for 14 consecutive days to induce premature ovarian failure in mice. Seventy-five mice with estrous cycle disorder were screened and randomly divided into 3 groups according to their body weight: model group, positive control group and hUCMSC group, and each group had 25 mice. Another 25 mice were used as negative controls. The mice in the hUCMSC group were injected with hUCMSCs in the tail vein, and the mice in the positive control group were given an oestradiol valerate solution and a medroxyprogesterone acetate solution in the tail vein. On the 1, 15, 30, 45, and 60 days after intravenous administration, vaginal smears were made to monitor the estrous cycles of the mice. The ovaries were weighed, and pathological sections were made to observe the morphology of the follicles; blood samples were collected to monitor the concentration of sex hormones (oestradiol and follicle-stimulating hormone).
The estrous cycles of the model group mice were disrupted throughout the experiment. Mice in the hUCMSC group and the positive control group resumed normal estrous cycles. The ovarian weight of the model group mice continued to decline. The ovarian weight of the hUCMSC group mice and the positive control group mice decreased first and then gradually increased, and the ovarian weight of the hUCMSC group mice was heavier than that of the positive control group mice. The difference was statistically significant ( < 0.05). Compared with the negative control group, the model group experienced a decrease in oestradiol and an increase in follicle-stimulating hormone, and the difference was statistically significant ( < 0.05). Compared with the model group, the hUCMSC and positive control groups experienced a slight increase in oestradiol and a decrease in follicle-stimulating hormone; the difference was statistically significant ( < 0.05). The pathological examination revealed that the mouse ovaries from the model group were atrophied, the volume was reduced, the cortical and medullary structures were disordered, the number of follicles at all stages was significantly reduced, the number of atretic follicles increased, the number of primordial follicles and corpus luteum significantly decreased, and the corpus luteum had an irregular shape. Compared with those of the model group, the lesions of the hUCMSC and positive control groups significantly improved.
hUCMSCs can repair ovarian tissue damaged by chemotherapy to a certain extent, can improve the degree of apoptosis in ovarian tissue, and can improve the endocrine function of mouse ovaries.
卵巢早衰(POI)和卵巢功能过早衰竭(POF)已成为威胁育龄期女性的主要问题之一。研究表明,从骨髓、脐带、外周血和羊水中移植的干细胞能够迁移并增殖至卵巢,促进卵巢功能修复,增加卵巢各级卵泡及颗粒细胞数量,改善内分泌功能,且在特定卵巢环境中可分化为卵母细胞,一定程度上恢复生育能力。
研究人脐带间充质干细胞(hUCMSCs)修复化疗后卵巢损伤的能力。
选取110只7 - 8周龄、体重16.0 - 20.0 g的雌性BALB/c小鼠。饲养至12周龄,连续14天腹腔注射环磷酰胺诱导小鼠卵巢早衰。筛选出75只出现发情周期紊乱的小鼠,按体重随机分为3组:模型组、阳性对照组和hUCMSC组,每组25只。另取25只小鼠作为阴性对照组。hUCMSC组小鼠经尾静脉注射hUCMSCs,阳性对照组小鼠经尾静脉给予戊酸雌二醇溶液和醋酸甲羟孕酮溶液。静脉给药后第1、15、30、45和60天,制作阴道涂片监测小鼠发情周期。称量卵巢重量,制作病理切片观察卵泡形态;采集血样监测性激素(雌二醇和促卵泡激素)浓度。
整个实验过程中,模型组小鼠发情周期紊乱。hUCMSC组和阳性对照组小鼠恢复正常发情周期。模型组小鼠卵巢重量持续下降。hUCMSC组和阳性对照组小鼠卵巢重量先下降后逐渐增加,且hUCMSC组小鼠卵巢重量重于阳性对照组小鼠。差异具有统计学意义(<0.05)。与阴性对照组相比,模型组雌二醇降低,促卵泡激素升高,差异具有统计学意义(<0.05)。与模型组相比,hUCMSC组和阳性对照组雌二醇略有升高,促卵泡激素降低;差异具有统计学意义(<0.05)。病理检查显示,模型组小鼠卵巢萎缩,体积减小,皮质和髓质结构紊乱,各阶段卵泡数量显著减少,闭锁卵泡数量增加,原始卵泡和黄体数量显著减少,黄体形态不规则。与模型组相比,hUCMSC组和阳性对照组病变明显改善。
hUCMSCs可一定程度修复化疗损伤的卵巢组织,可改善卵巢组织凋亡程度,可改善小鼠卵巢内分泌功能。