Menstrual blood derived mesenchymal stem cells combined with Bushen Tiaochong recipe improved chemotherapy-induced premature ovarian failure in mice by inhibiting GADD45b expression in the cell cycle pathway

Abstract

Background 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. Methods Twenty-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. Results Epirubicin 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. Conclusions MB-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.

Human mesenchymal stem cell treatment of premature ovarian failure: new challenges and opportunities

“…hMB-MSCs combined with Bushen Tiaochong recipe improved the ovarian function of epirubicin-induced mice with POF, which might be related to inhibiting the expression of GADD45b and promoting the expression of CyclinB1 and CDC2. This therapy combined with stem cells and other treatments also provided a new research direction in POF treatment [130]. Moreover, DiI-labeled hMB-MSCs were found to be localized in the GC layer of immature follicles.…”

Mesenchymal Stem Cells in Premature Ovarian Insufficiency: Mechanisms and Prospects

“…Human MSCs increase GCs proliferation, and inhibit their apoptosis by inhibiting expression of Gadd45b protein, which is involved in cell apoptosis ( Yan et al, 2019 ). Similarly, Guo et al (2019) showed that HuMenSCs combined with the Bushen Tiaochong recipe can rescue ovarian function by decreasing apoptosis of ovarian cells through modulating expression of Gadd45b, pCDC2, and CyclinB1. Moreover, Sun et al (2013) reported that ADSCs could increase oocyte and follicle number through gene-expression changes and through their paracrine effects.…”

Loss of ASPM Disrupts Female Folliculogenesis in Mice

“…The cytological assessment of vaginal smears, composed of samples obtained in the proestrus, estrus, metaestrus and diestrus stages, showed that the ovarian function was regulated by secretary hormones such as estrogen and progesterone [23,24]. The cyclicity was relatively irregular at 7-11 weeks old in both control and Aspm KO mice, which might be due to sexual immaturity, individual differences, and no exposure to male animals.…”