RESUMEN
Chemotherapeutic drugs can cause reproductive damage by affecting sperm quality and other aspects of male fertility. Stem cells are thought to alleviate the damage caused by chemotherapy drugs and to play roles in reproductive protection and treatment. This study aimed to explore the effects of human umbilical cord mesenchymal stem cells (hUC-MSCs) on alleviating paclitaxel (PTX)-induced spermatogenesis and male fertility defects. An in vivo PTX-induced mice model was constructed to evaluate the reproductive toxicity and protective roles of hUC-MSCs in male fertility improvement. A 14 day PTX treatment regimen significantly attenuated mice spermatogenesis and sperm quality, including affecting spermatogenesis, reducing sperm counts, and decreasing sperm motility. hUC-MSCs treatment could significantly improve sperm functional indicators. Mating experiments with normal female mice and examination of embryo development at 7.5 days post-coitum (dpc) showed that hUC-MSCs restored male mouse fertility that was reduced by PTX. In IVF experiments, PTX impaired sperm fertility and blastocyst development, but hUC-MSCs treatment rescued these indicators. hUC-MSCs' protective role was also displayed through the increased expression of the fertility-related proteins HSPA2 and HSPA4L in testes with decreased expression in the PTX-treated group. These changes might be related to the PTX-induced decreases in expression of the germ cell proliferation protein PCNA and the meiosis proteins SYCP3, MLH1, and STRA8, which were restored after hUC-MSCs treatment. In the PTX-treated group, the expression of testicular antioxidant proteins SIRT1, NRF2, CAT, SOD1, and PRDX6 was significantly decreased, but hUC-MSCs could maintain these expressions and reverse PTX-related increases in BAX/BCL2 ratios. hUC-MSCs may be a promising agent with antioxidant and anti-apoptosis characteristics that can maintain sperm quality following chemotherapy treatment.
Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Humanos , Masculino , Ratones , Femenino , Animales , Paclitaxel/efectos adversos , Paclitaxel/metabolismo , Antioxidantes/metabolismo , Cordón Umbilical , Motilidad Espermática , Semen , Espermatogénesis , FertilidadRESUMEN
OBJECTIVE: The objective of the present study was to explore the role of the inhibitor of apoptosis protein (IAP) Livin in radioresistance in nonsmall cell lung cancer (NSCLC). METHODS: Lung adenocarcinoma cell lines A549 and SPC-A1 were used for this study. Using the technique of molecular cloning and gene transfection, two Livin isoforms, Livinα and ß, respectively, were expressed in A549 cells with the purpose of exploring the role of Livin in radiation resistance of A549 cells. Moreover, a Livin-specific gene-silencing system was developed using SPC-A1 cell line with the purpose of increasing radiosensitivity of SPC-A1 cells. RESULTS: A549 cells were induced by radiation to express Livin isoforms, Livinα and ß. A549 cells expressed Livin isoforms stably after gene transfection and the transfected cells demonstrated characteristics of antiradiation. However, Livin gene-silenced SPC-A1 cells exhibited remarkably enhanced radiation sensitivity. CONCLUSION: The IAP Livin is an important molecule in antiradiotherapy of NSCLC. Livin-specific gene silencing is likely to be an effective means to enhance radiation sensitivity of lung cancer.