Bone marrow derived mesenchymal stem cells transplantation rescues premature ovarian insufficiency induced by chemotherapy

Abstract

Premature ovarian insufficiency (POI) is an important cause of infertility and also cause menopausal symptoms, which greatly reduced the quality of life for women. Hormone replacement therapy (HRT), as an important strategy, improved the quality of life for patients, however, the role of HRT in promoting fertility remains controversial. Therefore, seeking an optimal regime for POI becomes more urgent. In this study, we established POI model induced by CTX and BUS and utilized bone marrow derived mesenchymal stem cells (BM-MSCs) transplantation to treat the POI. We found that the decrease of estrogen and the increase of FSH induced by administration of CTX and BUS were rescued by BM-MSC transplantation. H&E staining and TUNEL assay showed that there were more healthy ovarian follicles and less apoptosis of ovarian cells after treatment with BM-MSCs. Further studies showed that there was an obvious decrease of Bax, p53, and p21 after transplantation, however, CyclinD2 was increased. In conclusion, our results demonstrated that BM-MSCs could restore injured ovarian function. Inhibiting apoptosis and promoting residual ovarian cell proliferation may contribute to the process.

Chinese abstract

早发性卵巢功能不全（POI）是不孕症的一个重要原因, 也会导致更年期综合征, 这会极大程度上降低女性的生活质量。激素补充治疗（HRT）作为一种重要的方法, 能够改善患者的生活质量, 但HRT对于提高生育力的作用仍存在争议。因此, 寻找治疗POI的最佳方法十分紧迫。本研究中, 我们通过环磷酰胺（CTX）和白消安（BUS）诱导建立POI模型, 并用骨髓源性间充质干细胞（BM-MSCs）治疗POI。我们发现BM-MSCs移植能够挽救CTX和BUS诱导的雌激素水平降低和FSH升高。HE染色和TUNEL检测显示BM-MSCs治疗后健康卵泡更多, 且卵巢细胞凋亡减少。进一步的研究显示移植后Bax, p53和p21显著减少, 但CyclinD2增加。因此, 我们的结果证实BM-MSCs能够修复损伤的卵巢功能。抑制凋亡和促进剩余卵巢细胞增殖可能有助于这一过程。

Keywords:

• POI
• BM-MSC
• transplantation
• apoptosis
• proliferation

Disclosure statement

The authors declare that there is no conflict of interest that would prejudice the impartiality of this scientific work.

Additional information

Funding

This study was supported by Jiangxi Science and Technology Support Project (20141BBG70065).