Small scale transcript expression profile of human first trimester placental villi analyzed by a custom-tailored cDNA array.
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Date
2010-07
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Abstract
Human placental trophoblastic mass grows rapidly between 4
and 8 weeks of gestation making it highly vulnerable to external and
internal challenges, however, there has been no reported study exploring
the developmental molecular characteristics in human first trimester
placental villi. In the present study, transcript expressions of human
placental villi of normal pregnancies during 6 (n=6), 7 (n=6) and 8 (n=6)
weeks of gestation using custom-tailored cDNA-based expression arrays
for ~400 annotated human gene products were examined. Unsupervised
and supervised analyses of expression data revealed that 386 (95%) genes
were overtly involved in the first trimester placental villi, and these genes
segregated into three clusters specifically corresponding to 6-, 7- and 8-
weeks of gestation in principal component analysis. Bayesian prediction
analysis based on relative expression levels of genes studied identified that
expression patterns in 15 samples out of 18 samples showed concordance
with high (0.8-1.0) confidence measures with the chronological age of the
placenta, however, two samples collected during 7-weeks of gestation and
one sample collected during 8-weeks of gestation were predicted to be 6-
weeks sample with confidence measures between 0.6 and 0.5. Unsupervised
hierarchical clustering analysis segregated the samples into two major
branches; while one of them was composed of five 7-weeks samples only,
the second major branch had three sub-branches: one of them was
exclusively composed of three 8-week samples only, while other two subbranches
were mainly composed of 6-weeks samples. K-means clustering
analysis identified four optimal clusters of genes depending on the similarity
of their relative expression for the set of genes studied across all the
samples. Gene ontology (GO) based functional classifications of genes in
K-means clusters revealed that the overall putative functions of co-regulated
gene clusters were mutually comparable, however, specific genes related
to ion homeostasis, metabolism, and VEGF activity specifically clustered in
8-weeks samples. Analysis of relative gene expression during in 6-8 weekplacental villi revealed that a large number of gene products were over
represented by their either up-regulation (70 genes: ~18%) or down
regulation (53 genes; ~14%) between 6 and 8 weeks villi samples and these
genes are reportedly involved in biological processes like regulation of cell
growth and proliferation, anti-apoptosis, angiogenesis, immune and
inflammatory responses, extracellular matrix remodeling and multicellular
organismal development involving almost all cellular components and
molecular functions like signal transduction activity, transcription factor
activity, nucleotide and protein binding, ion (especially calcium and zinc)
binding and growth receptor activities. Interestingly, four genes (oxytocin
receptor, tenascin C, TNF-R1 and retinol binding protein 1) showed
differential regulation in human placental villi during 6-8 weeks of gestation,
suggestive of an underlying network of regulation involving these factors
in the developing placenta. To our knowledge, this is the first report
indicating that these genes are involved in the early stage development of
human placenta.
Description
Keywords
early placenta villi, gene expression, transcriptomics
Citation
Khan M A, Kar M, Mittal S, Kumar S, Bharagava V L, Sengupta J, Ghosh D. Small scale transcript expression profile of human first trimester placental villi analyzed by a custom-tailored cDNA array. Indian Journal of Physiology and Pharmacology. 2010 Jul-Sept; 54(3): 235-254.