Abstract
Premature ovarian failure (POF) is one of the principal causes of female infertility, and although its causes are complex and diverse, autoimmune deficiency may be involved. Human umbilical cord mesenchymal stem cells (UCMSCs) can be used for tissue regeneration and repair. Therefore, the present study was designed to determine the role of UCMSCs in immune factor-induced POF in rats. In this study, different concentrations of UCMSCs were injected into induced POF rats. Ovarian functions were examined by evaluating the estrus cycle, follicular morphology, hormonal secretion, and the proliferation and apoptosis of granulosa cells. Our results showed that the estrus cycle of rats returned to normal and follicular development was significantly improved after transplantation of UCMSCs. In addition, serum concentrations of 17-estradiol (E2), progesterone (P4), and anti-Müllerian hormone (AMH) increased significantly with treatment. Transplantation of UCMSCs also reduced the apoptosis of granulosa cells and promoted the proliferation of granulosa cells. All of these improvements were dose dependent. Furthermore, the results of related gene expression showed that transplanted human UCMSCs upregulated the expression of Bcl-2, AMH, and FSHR in the ovary of POF rats and downregulated the expression of caspase-3. These results further validated the potential mechanisms of promoting the release of cell growth factors and enhancing tissue regeneration and provide a theoretical basis for the clinical application of stem cells in the treatment of premature ovarian failure.
Highlights
As previously reported, many women suffer from premature ovarian failure (POF) before the age of forty, concomitant with amenorrhea, ovarian atrophy, low estrogen levels, and high levels of gonadotropins [1,2,3,4]
We established a rat model of POF by injecting ovarian antigens into the rat subcutaneously, and via tail vein transplantation of umbilical cord mesenchymal stem cells (UCMSCs), we confirmed their use as a cell therapy tool in the treatment of POF, and we demonstrated that the therapeutic effect was commensurate with increasing UCMSC concentrations
The UCMSCs were small round cells that gradually became larger in culture became fusiform, polygonal, and spindle-shaped
Summary
Many women suffer from premature ovarian failure (POF) before the age of forty, concomitant with amenorrhea, ovarian atrophy, low estrogen levels, and high levels of gonadotropins [1,2,3,4]. POF is caused by multiple factors, including heritage defects, autoimmunity, and environmental toxicity [5, 6]. The pathologic characterizations of autoimmune ovarian disease (AOD) include inflammation, atrophy, and serum autoantibodies to ovarian antigens [8]. A POF model has been established using autoimmune ovarian inflammation by injecting ovarian antigens into rats. The incidence of POF has shown an increasing trend in recent years, with younger women afflicted. The Women’s Health Initiative (WHI) has revealed that the traditional treatment with hormone replacement therapy (HRT) could increase the incidence of breast cancer, endometrial cancer, cardiovascular disease, and stroke [9]. It is of paramount importance to find a safer treatment for POF
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