Endometrial mesenchymal stem cells isolated from menstrual blood repaired epirubicin-induced damage to human ovarian granulosa cells by inhibiting the expression of Gadd45b in cell cycle pathway

月经血中分离的子宫内膜间充质干细胞通过抑制细胞周期通路中 Gadd45b 的表达修复表柔比星引起的人卵巢颗粒细胞损伤

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作者:Zhongrui Yan, Fengyi Guo, Qing Yuan, Yu Shao, Yedan Zhang, Huiyan Wang, Shaohua Hao, Xue Du

Background

To explore the effect of mesenchymal stem cells isolated from menstrual blood (MB-MSCs) on epirubicin-induced damage to human ovarian granulosa cells (GCs) and its potential mechanisms.

Conclusions

MB-MSCs repaired epirubicin-induced damage to GCs, which might be related to the inhibition of Gadd45b protein expression.

Methods

The estradiol, progesterone, anti-Müllerian hormone, inhibin A, and inhibin B levels were determined using enzyme-linked immunosorbent assay. The proliferation of GCs was detected by Cell Counting Kit-8 assays. The cell cycle distribution was detected by propidiumiodide single staining. The apoptosis of GCs was determined using Annexin V and 7-AAD double staining. The differentially expressed genes of GCs were analyzed with Affymetrix Human Transcriptome Array 2.0 gene chip and verified with Western blot analysis.

Results

Epirubicin inhibited the secretion of estradiol, progesterone, anti-Müllerian hormone, inhibin A, and inhibin B and the proliferation of GCs; arrested these GCs in G2/M phase; and promoted the apoptosis of GCs. However, MB-MSCs repaired epirubicin-induced damage to GCs. Differentially expressed genes of GCs, Gadd45b, CyclinB1, and CDC2, were found by microarray and bioinformatics analysis. Western blot showed that epirubicin upregulated Gadd45b protein expression and downregulated CyclinB1 and CDC2 protein expression, while MB-MSCs downregulated Gadd45b protein expression and upregulated CyclinB1 and CDC2 protein expression. Conclusions: MB-MSCs repaired epirubicin-induced damage to GCs, which might be related to the inhibition of Gadd45b protein expression.

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