RESUMO
OBJECTIVE: To evaluate the effects of resveratrol on oocyte maturation in aged mice and humans. DESIGN: Experimental laboratory study. SETTING: University-based reproductive medicine center. PATIENT(S): A total of 64 women 38-45 years of age undergoing intracytoplasmic sperm injection (ICSI) and 48-52-week-old female C57BL/6J mice. INTERVENTION(S): In vitro culture in the presence of three different concentrations of resveratrol (0.1, 1.0, and 10 µm) or dimethylsulfoxide. MAIN OUTCOME MEASURE(S): Parameters of oocyte nuclear maturation, fertilization, immunofluorescence intensity of mitochondria, and normal morphology of spindle and chromosome of oocytes undergoing in vitro maturation (IVM) in aged mice and humans; blastocyst formation and levels of SRIT1, CAT, SOD1, and GPX4 gene expressions in aged mice. RESULT(S): Resveratrol at 1.0 µm significantly increased first polar body emission rate in oocytes derived from aged mice and humans, and an increased percentage of fertilization and blastocyst formation was observed in aged mice. In addition, immunofluorescence intensity of mitochondria and normal morphology of spindle and chromosome of oocytes undergoing IVM were notably improved compared with control samples in aged mice and human. Furthermore, the use of resveratrol exhibited enhanced expression patterns of SRIT1, CAT, SOD1, and GPX4 in aged mice. CONCLUSION(S): Resveratrol induced oocyte maturation and blastocyst formation in aged mice, and improved oocyte maturation and quality was examined in aged humans. In conclusion, 1.0 µm resveratrol was the appropriate concentration in IVM medium.
Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/farmacologia , Técnicas de Maturação in Vitro de Oócitos/métodos , Oócitos/efeitos dos fármacos , Oócitos/crescimento & desenvolvimento , Resveratrol/farmacologia , Adulto , Envelhecimento/fisiologia , Animais , Relação Dose-Resposta a Droga , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Indução da Ovulação/métodosRESUMO
CDGSH iron sulfur domain 2 (CISD2) has been found to be important in carcinogenesis. However, the role of CISD2 in glioma remains to be elucidated. The present study aimed to investigate the role of CISD2 in glioma using the reverse transcriptionquantitative polymerase chain reaction, western blotting, coimmunoprecipitation assay, immunofluorescence staining and other methods. The results demonstrated that the mRNA and protein levels of CISD2 were found to be upregulated in glioma tissues, compared with the levels in matched normal tissues. Clinical data analysis showed that the level of CISD2 was negatively correlated with the survival rates of patients with glioma. In addition, high levels of CISD2 were associated with advanced clinical stage, relapse, vascular invasion and increased tumor size. The inhibition of CISD2 suppressed the proliferation and survival of glioma cells in vitro and in vivo. Mechanistically, it was found that small interfering RNAinduced knock down of CISD2 inhibited the proliferation of glioma cells through activating beclin1mediated autophagy. The results also revealed that CISD2 was a target of microRNA (miR)449a. Together, the results of the present study demonstrated that CISD2 was increased in glioma samples and was associated with poor prognosis and aggressive tumor behavior. The miR449a/CISD2/beclin1mediated autophagy regulatory network contributed to the proliferation of glioma cells. Targeting this pathway may be a promising strategy for glioma therapy.