Metabolic gene profile in early human fetal heart development.

The primitive cardiac tube starts beating 6-8 weeks post fertilization in the developing embryo. In order to describe normal cardiac development during late first and early second trimester in human fetuses this study used microarray and pathways analysis and created a corresponding 'normal' database. Fourteen fetal hearts from human fetuses between 10 and 18 weeks of gestational age (GA) were prospectively collected at the time of elective termination of pregnancy. RNA from recovered tissues was used for transcriptome analysis with Affymetrix 1.0 ST microarray chip. From the amassed data we investigated differences in cardiac development within the 10-18 GA period dividing the sample by GA in three groups: 10-12 (H1), 13-15 (H2) and 16-18 (H3) weeks. A fold change of 2 or above adjusted for a false discovery rate of 5% was used as initial cutoff to determine differential gene expression for individual genes. Test for enrichment to identify functional groups was carried out using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Array analysis correctly identified the cardiac specific genes, and transcripts reported to be differentially expressed were confirmed by qRT-PCR. Single transcript and Ontology analysis showed first trimester heart expression of myosin-related genes to be up-regulated >5-fold compared with second trimester heart. In contrast the second trimester hearts showed further gestation-related increases in many genes involved in energy production and cardiac remodeling. In conclusion, fetal heart development during the first trimester was dominated by heart-specific genes coding for myocardial development and differentiation. During the second trimester, transcripts related to energy generation and cardiomyocyte communication for contractile coordination/proliferation were more dominant. Transcripts related to fatty acid metabolism can be seen as early as 10 weeks and clearly increase as the heart matures. Retinol receptor and gamma-aminobutyric acid (GABA) receptor transcripts were detected, and have not been described previously in human fetal heart during this period. For the first time global gene expression of heart has been described in human samples to create a database of normal development to understand and compare with known abnormal fetal heart development.

Differential changes in gene expression in human brain during late first trimester and early second trimester of pregnancy.

OBJECTIVE: This study aimed to describe brain development during the first (B1) and second trimester (B3) in human fetuses. DESIGN: Ten brains from 10 to 18 weeks of gestational age (GA) were collected, and the RNA was used for transcriptome analysis (Affymetrix 1.0 ST microarray chip). Differences in brain development within 10 to 18 GA were investigated by dividing the sample into 10 to 12 (B1), 13 to 15(B2) and 16 to 18(B3) weeks. A fold change of 2 or above, with a false discovery rate of 5%, was used as cut-off to determine differential gene expression for individual genes. Quantitative real-time PCR was used to confirm differences. Tests for enrichment procedures (using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) were then used to identify functional groups of mRNA. RESULTS: At 10 to 12 weeks, brains showed neuronal migration to be upregulated. From 10 to 18 weeks, brains showed genes coding for neuronal migration, differentiation and connectivity upregulated. ALDH1A1 and NPY genes, marker of spinal cord and striatum, were upregulated in B1 and B3 brains, respectively. Also, SLITRK6-HAS2 and CRYAB-PCDH18 genes for ear and eye sensory input were upregulated in B1. CONCLUSIONS: For the first time, brain global gene expression was described in human samples. Period B1 was dominated by genes coding for neuronal migration, differentiation, programmed cell death and sensory organs. B3 was dominated by neuronal proliferation, branching and myelination. Creating such a database will allow comparison with abnormals in future studies.