Abstract
BackgroundTo 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.MethodsTwenty-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.ResultsEpirubicin 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.ConclusionsMB-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.
Highlights
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
We studied the effect and the relevant mechanisms of MB-MSCs combined with BSTCR on the ovarian function after epirubicin chemotherapy in mice and compared the efficacy of the combined treatment with MB-MSCs or BSTCR treatment, respectively
We found that combined with BSTCR, MB-MSCs could result in the recovery of the estrous cycle, an increase in the number of promordial, primary, secondary and antral follicles, a decrease in the number of atretic follicles and ovarian cell apoptosis, an increase in serum E2 and anti-Müllerian hormone (AMH) levels, and a reduction in serum follicle-stimulating hormone (FSH) levels in epirubicin induced POF mice
Summary
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. Chemotherapy has the potential to increase the survival of patients with malignant tumors, but concerns have been raised about chemotherapy-induced decrease in ovarian function in young patients Cancer patients such as breast cancer, leukemia and lymphoma are usually diagnosed at young ages and the lifetime is prolonged after chemotherapy. Amenorrhea and infertility caused by chemotherapy has gradually been paid attention to [1,2,3] Anthracycline antibiotics such as doxorubicin and epirubicin are the first-line chemotherapeutic agents for the treatment of acute leukemia, lymphoma and breast cancer. It was reported that anthracycline- and taxanebased chemotherapy was associated with a 40–60% risk of treatment-induced POF in breast cancer patients under the age of 40 years [6], but the mechanism of ovarian toxicity remains unclear. The ovarian toxicity of epirubicin has rarely been reported
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