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MRNA expression profiles of Neural Tube Defects (NTDs) in the 2nd trimester of human fetus

ABSTRACT: Neural Tube Defects (NTDs) are serious health problems of infants, accounting for large proportion of live birth defects in infants and miscarriage in women worldwide. Although some epidemiologic studies suggest both genetic and environmental factors were involved in the progression of the diseases, the etiologies of NTDs are not well understood at present. The objective of our study was to generate and to compare mRNA profiles of NTDs with those of normal controls in the 2nd trimesters of pregnancy. Illumina microarray chips (beadarrays) were utilized to identify the altered mRNA transcripts in the organ samples recruited from Luliang Prefecture in Shanxi Province, China, which has the highest occurrence of NTDs in world. The beadarrays identified 101 un-regulated and 194 down-regulated mRNA transcripts in the NTDs compared with the controls in the spinal cord. A number of genes in the cholesterol biosynthesis pathway were down-regulated. In particular, SIRT2, a key regulator of cholesterol biosynthesis, was significantly down-regulated in NTD samples. Our findings provide evidences that, the decrease of cholesterol biosynthesis in the spinal cord of NTD may affect the neural tube closure in the affected fetuses.

ORGANISM(S): Homo sapiens

PROVIDER: GSE33111 | GEO | 2019/10/10

REPOSITORIES: GEO

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Project description:Maternal folic acid intake is crucial for the development of the offspring's nervous system, and folic acid metabolism disorders during pregnancy lead to neural tube defects (NTDs) in the fetus. Folic acid and vitamins biosynthesis is a major biochemical feature of gut microbiota. The complex and diverse microbial ecosystem residing within maternal host contributes critically to these intergenerational impacts. However, the mechanisms still require further investigation. In this study, we found that the low folate diets combined MTX-induced changed the structure/composition of the gut microbiota and substantially altered the fecal metabolic phenotype of pregnant mice, including central carbon metabolism in cancer and vitamin digestion & absorption. We demonstrated that the correlation betweent gut microbiota of pregnant mice and the brain metabolic profiles of NTDs fetal mice. According to our data, the Lactobacillales and Bifidobacteriales abundances in pregnant mice gut were positively correlated with the abundances of lipid metabolites in fetal mice brain. The abundances of Enterobacterales and Clostridiales were negatively correlated with those lipid metabolites. Interestingly, the abundance of Inosine, Uridine, L-Carnitine and Glycerophosphocholine were down-regulated synchronously in pregnant feces and NTDs fetal mice brain. This was probably the intergenerational microbial-metabolism biomarkers of NTDs. Our study provides evidence for how perinatal microecological factors shape fetal neural tube development. Feces metabolomics is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS4893' rel='noopener noreferrer' target='_blank'>MTBLS4893</a>.Brain tissue metabolomics is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS4894' rel='noopener noreferrer' target='_blank'>MTBLS4894</a>.

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MRNA expression profiles of Neural Tube Defects (NTDs) in the 2nd trimester of human fetus

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