Antenatal steroid (AS) adversely affects placental function: A study of molecular effects using micro-array analysis

Antenatal steroids (AS) are used to augment fetal lung maturity and there is a major concern that they impair fetal growth. If delivery is delayed after using AS, placental function and hence fetal growth may be compromised even further. We treated three pairs of pregnant C57/BL mice with AS and studied changes in placental gene expression by microarray analysis, these results were later confirmed by semi quantitative RT-PCR, in situ hybridization and Oligo ApopTaq assay. AS treated placentas were hydropic, friable and pale. Placental weight was decreased (78.8±16.7 mg compared to 81.3±17 mg, p<0.05) and so was fetal weight (914 38 mg compared to 1160 85 mg, p<0.05). There was more than 99% similarity between the three gene chip data sets. AS led to down-regulation of 1212 genes and up-regulation of 1382 genes. AS led to decrease in expression of genes involved in cell division like cyclin A2, B1, D2, CDK2, CDK4 and M phase protein kinase along with growth promoting genes like BMP4 and IGF-BP4. Tryptophan hydroxylase gene a key regulator of serotonin production was upegulated by >15 fold. AS treatment caused deleterious effects on placenta by decreasing expression of growth related genes and increased apoptosis of trophoblast cells. Keywords: comparitive gene expression 3 sets of pregnant C57/BL mice were treated with dexamethasone (0.5 mg/kg) on gestational day 15, 16, 17. 3 sets of pregant mice were injected with saline and served as controls.