Translational medicine is an emerging idea in current medical research area. Typically, for the purpose of bridging the gap between basic and clinical research, it not only emphasizes the urgency and necessity to break the traditional working formats, including single subject centered research team and limited cooperation among different scientific groups, but also highlights a more close and frequent interaction between basic scientist and clinician. In order to reach this goal, the theory and method of systems biology should be employed. This paper mainly focused on a central issue that how to carry out an investigation on early clinical diagnosis of xenobiotic-induced intrauterine growth retardation (IUGR) by using research concept of translational medicine and method of systems biology. Briefly, a hypothesis of common mechanism of IUGR was first proposed and subsequent validation was performed via integrating--omics (e.g. genomics, proteomics, cytomics, metabonomics/metabolomics) and molecular biology techniques. Metabonomics was further utilized to explore IUGR biomarker and establish preliminary forecasting model by bioinformatics and computational biology, which is available for early diagnosis of IUGR and make a complement to current evaluation criteria.
Biomarkers ; analysis ; Computational Biology ; Early Diagnosis ; Female ; Fetal Growth Retardation ; chemically induced ; diagnosis ; metabolism ; Genomics ; Humans ; Metabolomics ; Pregnancy ; Proteomics ; Systems Biology ; Translational Medical Research ; Xenobiotics ; toxicity

Animals ; Caffeine/adverse effects* ; Central Nervous System Stimulants/adverse effects* ; Dose-Response Relationship, Drug ; Female ; Fetal Growth Retardation/chemically induced* ; Immune System Diseases/chemically induced* ; Male ; Organ Size/drug effects* ; Pregnancy ; Pregnancy Complications/immunology* ; Rats ; Spleen/growth & development*

OBJECTIVETo study the effects of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) on the development of fetal rats and to explore the relationship between TCDD-induced abnormal development in rats and the expression and the methylation of insulin-like growth factor 2 gene (Igf2).

METHODSA single dose of 10 microg/kg TCDD was given to gestation day (GD) 10 pregnant rats by gavage. On GD20, the fetuses were taken out and examined. The crown-rump length, the body weight and the placental weight were measured. The expression of Igf2 in liver was detected by real-time quantitative reverse transcription (RT-PCR) and Western blot. The methylation of Igf2 differentially methylated regions (DMRs) in liver was analyzed by a methylation-sensitive restriction enzyme Hpa II PCR assay and a bisulfite-modified DNA sequencing procedure.

RESULTSIn the treatment group, 12.2% of the fetuses were either dead or absorbed, and 11.6% of them were malformed. For the live fetuses, their crown-rump length, body weight and placental weight were significantly lower than those of the control group. The relative amount of Igf2 mRNA in the treated livers and the control livers was 0.77 +/- 0.11 and 0.27+/- 0.15, respectively. The number was significantly higher in the treatment group than in the control group (P < 0.01). Western blot also showed a remarkable up regulation of Igf2 protein in liver after treatment. The two groups showed no difference in the methylation status of Igf2 DMR1 in liver. The DMR2 Igf2 was significantly hypomethylated in the treated livers than in the control livers.

CONCLUSIONExposure to TCDD in pregnancy can lead fetal rats to death, absorption, malformation and intrauterine growth retardation (IUGR). The TCDD led abnormal development in rats may be associated with the hypomethylated DMR2 of Igf2 and the up regulation of Igf2 in liver.

Animals ; Blotting, Western ; DNA Methylation ; Female ; Fetal Growth Retardation ; chemically induced ; genetics ; metabolism ; Gene Expression ; drug effects ; Insulin-Like Growth Factor II ; genetics ; metabolism ; Polychlorinated Dibenzodioxins ; toxicity ; Pregnancy ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo study the effect of behavioral training on the learning and memory abilities and changes of NR2B and GluR1 expressions in the hippocampus of offspring rats with fetal growth retardation (FGR).

METHODSA FGR model was established in SD rats by passive smoking. The offspring rats were divided into FGR group and control group, each then randomized into training and untrained group. Morris water maze behavioral training was carried out in postnatal months 2 and 4, and the learning and memory abilities of the young rats were assessed using dark-avoidance test and step-down test. NR2B and GluR1 expression in the hippocampus of the rats were detected by immunohistochemistry.

RESULTSIn the dark-avoidance and step-down tests, the FGR rats showed deteriorated learning and memory performance in comparison with the control group, but behavioral training resulted in improved performance of the rats. The performance in FGR group was much improved after behavioral training, and the model factor and the training factor showed a significant interaction (P<0.05). The expression of NR2B and GluR1 in CA1 and CA3 regions of the hippocampus decreased in FGR group, then the their expressions in the CA1 region increased after training in both FGR and control groups, and the increment was especially obvious in GluR1 expression in the CA1 region at postnatal month 2. The two factors showed a significant interaction (P<0.05).

CONCLUSIONBehavioral training can improve the learning and memory abilities of FGR offspring rats, the mechanism of which is probably related to increased expression of NR2B and GluR1 in the CA1 region of the hippocampus.

Animals ; Animals, Newborn ; Avoidance Learning ; Behavior, Animal ; Female ; Fetal Growth Retardation ; chemically induced ; physiopathology ; Hippocampus ; metabolism ; Male ; Memory ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA ; genetics ; metabolism ; Receptors, N-Methyl-D-Aspartate ; genetics ; metabolism ; Tobacco Smoke Pollution