RESUMO
Polychlorinated biphenyls (PCBs) are a class of organic pollutants that have been widely found in the environment. The chemical 2,3',4,4'5-pentachlorobiphenyl (PCB118) is an important dioxin-like PCB compound with strong toxicity. PCB118 can accumulate in adipose tissue, serum and milk in mammals, and it is highly enriched in the follicular fluid. In this study, pregnant mice were exposed to 0, 20 and 100 µg/kg/day of PCB118 during pregnancy at the fetal primordial germ cell migration stage. The methylation patterns of the imprinted genes H19, Snrpn, Peg3 and Igf2r as well as the expression levels of Dnmt1, 3a, 3b and 3l, Uhrf1, Tet2 and Tet3 in fully grown germinal vesicle oocytes were measured in offspring. The rates of in vitro maturation, in vitro fertilization, oocyte spindle and chromosomal abnormalities were also calculated. The results showed that prenatal exposure to PCB118 altered the DNA methylation status of differentially methylated regions in some imprinted genes, and the expression levels of Dnmt1, 3a, and 3l, Uhrf1 and Tet3 were also changed. In addition, PCB118 disturbed the maturation process of progeny mouse oocytes in a dose-dependent manner. Therefore, attention should be paid to the potential impacts of PCB118-contaminated dietary intake during pregnancy on the offspring's reproductive health.
Assuntos
Poluentes Ambientais/toxicidade , Impressão Genômica/efeitos dos fármacos , Oócitos/efeitos dos fármacos , Oogênese/efeitos dos fármacos , Bifenilos Policlorados/toxicidade , Efeitos Tardios da Exposição Pré-Natal/genética , Animais , Animais Recém-Nascidos , Metilação de DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Epigênese Genética/efeitos dos fármacos , Feminino , Exposição Materna/efeitos adversos , Camundongos , Oócitos/crescimento & desenvolvimento , Oogênese/genética , GravidezRESUMO
INTRODUCTION: The objective of the study was to develop a panel of microRNAs (miRNAs) as highly sensitive and specific biomarkers for lung cancer early detection. MATERIALS AND METHODS: The study contained 2 phases: first, preliminary marker selection based on previous reports on the serum of 24 early stage lung cancer patients and 24 healthy control subjects by TaqMan probe-based real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR); and second, validation of miRNA markers on 94 early stage lung cancer, 48 stage III to IV lung cancer, and 111 healthy control serum samples. RESULTS: A total of 3 miRNAs (miR-125a-5p, miR-25, and miR-126) were selected for further analysis in this study. The combination of the 3 miRNAs could produce 0.936 area under the receiver operating characteristic curve value in distinguishing early stage lung cancer patients from control subjects with 87.5% sensitivity and 87.5% specificity, respectively. The diagnostic value of the miRNA panel in an independent set of lung cancer patients confirmed the sensitivity and specificity. CONCLUSION: The results demonstrated that the panel of miRNA biomarkers had the potential for the early detection of lung cancer.