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Open Access Research article

BMSCs reduce rat granulosa cell apoptosis induced by cisplatin and perimenopause

Jun-qi Guo, Xia Gao, Zhi-jie Lin, Wei-zhen Wu, Liang-hu Huang, Hui-yue Dong, Jin Chen, Jun Lu, Yun-fen Fu, Jin Wang, Yu-jie Ma, Xiao-wen Chen, Zhi-xian Wu, Fu-qiang He, Shun-liang Yang, Lian-ming Liao, Feng Zheng and Jian-ming Tan*

Author Affiliations

Organ Transplant Institute, Fuzhou General Hospital, DongFang Hospital of Xiamen University and Fujian Key Laboratory of Transplant Biology, Fujian, 350025, PR. China

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BMC Cell Biology 2013, 14:18  doi:10.1186/1471-2121-14-18

Published: 19 March 2013

Abstract

Background

The objective of this study was to evaluate the effect of bone marrow mesenchymal stem cells (BMSCs) on the apoptosis of granulosa cells (GCs) in rats.

BMSCs and GCs were isolated from rats. GCs were separated into one of the following three groups: an untreated control group (control), a cisplatin (5 mg/L) treatment group (cisplatin), and group co-cultured with BMSCs and treated with cisplatin (BMSC). GC apoptosis was analyzed by annexin V staining and real-time PCR analysis for apoptosis-related genes. The effect of BMSCs was also determined in 9 to 10 month-old perimenopausal rats that were separated into the following groups: saline control, BMSC transplantation (1–2 × 106 cells), and estrogen treatment (0.158 mg/kg/d) groups. A young group consisting of 3 to 4 month-old rats that were treated with saline was also evaluated as a control. After 1 and 3 months, GC apoptosis was evaluated by TUNEL analysis.

Results

Cisplatin increased GC apoptosis from 0.59% to 13.04% in the control and cisplatin treatment groups, respectively, which was significantly reduced upon co-culture with BMSCs to 4.84%. Cisplatin treatment increased p21 and bax and decreased c-myc mRNA expression, which was reversed upon co-culture with BMSCs. As compared to young rats, increased apoptosis was observed in the perimenopausal rats (P < 0.001). After 3 months, the apoptosis rate in the BMSC group was significantly lower than that of the control group (P = 0.007).

Conclusions

BMSC therapy may protect against GC apoptosis induced by cisplatin and perimenopause. Further studies are necessary to evaluate therapeutic efficacy of BMSCs.

Keywords:
Bone marrow mesenchymal stem cells; Granulosa cells; Apoptosis; Ovary; Rat; Perimenopause