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Menstrual blood derived mesenchymal stem cells combined with Bushen Tiaochong recipe improved chemotherapy-induced premature ovarian failure in mice by inhibiting GADD45b expression in the cell cycle pathway.
Reproductive Biology and Endocrinology ( IF 4.2 ) Pub Date : 2019-07-16 , DOI: 10.1186/s12958-019-0499-2
Fengyi Guo 1 , Tian Xia 2 , Yedan Zhang 1 , Xiaotong Ma 1 , Zhongrui Yan 1 , Shaohua Hao 1 , Yali Han 1 , Ruihong Ma 2 , Yuan Zhou 3 , Xue Du 1
Affiliation  

BACKGROUND To investigate the therapeutic effects of menstrual blood derived mesenchymal stem cells (MB-MSCs) combined with Bushen Tiaochong recipe (BSTCR) on epirubicin induced premature ovarian failure (POF) in mice. METHODS Twenty-four female C57BL/6 mice of 6-8 weeks were intraperitoneally injected with epirubicin to induce POF, and then they were randomized into 4 groups of 6 mice each and treated with PBS, MB-MSCs, BSTCR, and MB-MSCs combined with BSTCR, respectively. Six mice of the same age were used as controls. Vaginal smear, TUNEL and hematoxylin-eosin staining were to observe estrous cycles, ovarian cell apoptosis and follicles. Enzyme-linked immunosorbent analysis determined serum estradiol, follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH) levels. RT-qPCR and Western Blot analysis were to determine GADD45b, CyclinB1, CDC2 and pCDC2 expressions. RESULTS Epirubicin treatment resulted in a decrease in the number of primordial, primary, secondary and antral follicles, an increase in the number of atretic follicles and ovarian cell apoptosis, a decrease in estradiol and AMH levels, an increase in FSH levels, and estrous cycle arrest. However, MB-MSCs combined with BSTCR rescued epirubicin induced POF through down-regulating GADD45b and pCDC2 expressions, and up-regulating CyclinB1 and CDC2 expressions. The combined treatment showed better therapeutic efficacy than BSTCR or MB-MSCs alone. CONCLUSIONS MB-MSCs combined with BSTCR improved the ovarian function of epirubicin induced POF mice, which might be related to the inhibition of GADD45b expression and the promotion of CyclinB1 and CDC2 expressions. The combined treatment had better therapeutic efficacy than BSTCR or MB-MSCs alone.

中文翻译:

经血来源的间充质干细胞与补肾调充方药合用可通过抑制细胞周期途径中GADD45b的表达来改善化疗诱导的小鼠卵巢早衰。

背景研究月经血来源的间充质干细胞(MB-MSCs)与补肾调冲方(BSTCR)联合对表柔比星诱导的卵巢早衰(POF)的治疗作用。方法对24只6-8周的雌性C57BL / 6小鼠腹膜内注射表柔比星诱导POF,然后将它们随机分为4组,每组6只小鼠,分别用PBS,MB-MSC,BSTCR和MB-MSC处理分别与BSTCR结合。将六只相同年龄的小鼠用作对照。阴道涂片,TUNEL和苏木精-伊红染色观察发情周期,卵巢细胞凋亡和卵泡。酶联免疫吸附分析确定了血清雌二醇,促卵泡激素(FSH)和抗苗勒勒激素(AMH)的水平。RT-qPCR和Western Blot分析确定GADD45b,CyclinB1,CDC2和pCDC2表达。结果表柔比星治疗导致原始,初级,继发和肛门窦卵泡数量减少,无定形卵泡数量和卵巢细胞凋亡增加,雌二醇和AMH水平降低,FSH水平增加,以及发情周期逮捕。但是,MB-MSC与BSTCR的结合通过下调GADD45b和pCDC2的表达以及上调CyclinB1和CDC2的表达来挽救表柔比星诱导的POF。联合治疗显示出比单独的BSTCR或MB-MSC更好的治疗效果。结论MB-MSC与BSTCR联合可改善表柔比星诱导的POF小鼠的卵巢功能,这可能与抑制GADD45b的表达以及促进CyclinB1和CDC2的表达有关。
更新日期:2019-07-16
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