Expressional regulation of genes linked to immunity & programmed development in human early placental villi.

BACKGROUND & OBJECTIVES: During 6 to 8 wk of gestation, human placental villi show a complex pattern of morphogenesis. There is however, no large scale gene expression study exploring the temporal pattern of the developmental molecular networks in placental villi during the early weeks of gestation. We evaluated the transcriptome profiling of humn placental villus samples obtained from fertile women with voluntarily terminated normal pregnancies between 6-8 wk of gestation.

METHODS: Transcriptomic profiles of individual human placental villous samples from 25 women with normal pregnancies during 6 to 8 wk of gestation were examined using human whole genome expression arrays. Quantitative RT-PCR validation of copy numbers of transcripts for selected 15 genes and exploratory analysis of the microarray data revealed a high degree of quality assurance supportive of further clustering and differential analyses. Immunoblot and immunohistochemical analysis of selected five candidate proteins (CAGE1, CD9, SLC6A2, TANK and VEGFC) based on transcript profiles were done to assess the pattern of down stream informational flow.

RESULTS: A large number (~9K) of genes with known functions were expressed in the experimental samples. The clustering analysis identified three major expression clusters with gestational age, and four co-expressional clusters. Differential analysis identified a highly discrete regulatory process involving only about 160 genes. Immunochemical analysis of selected candidate proteins based on transcript profiles revealed generally synchronous expression in human early placental villi.

INTERPRETATION & CONCLUSIONS: Several signaling pathways linked to immunity (COL1, JAK2, JAK3, IL12, IL13, IL15, IL27, STAT3 and STAT5) were downregulated, while genes of the enriched category of antiviral immunity (ATF/AP1, IL10R and OAS) were clearly over-expressed. Transcriptional integration supportive of programmed development was observed in first trimester placental villi and it included regulation of apoptosis and cell cycle progression (ARRB1, ATR, BLM, CHRNA7, CHRNB1, FYN, KPNA4, and MTOR/FRAP), autophagy (ATG4B, ATG14, BAD, and BCL2), cell adhesion (CD9 and FN1) and epithelial-to-mesenchymal transition (CALD1, FN1, HEY1, MMP2, and WNT3A).