@entity519 induced XXXX /HIF-2 activity alters trophoblast transcriptional regulation and promotes invasion.

@entity7738 @entity3334 @entity8090 @entity71053 @entity2301 @entity26 @entity32299 @entity2032 @entity519 @entity71054
UNASSIGNED: Reduced or absent cytotrophoblast invasion of the maternal uterine spiral arterioles is a common clinical finding in studies of pregnancies complicated by preeclampsia, suggesting that the mechanisms mediating invasion of these cells is perturbed. The placenta initially develops in a low @entity26 environment of 1-2% @entity26 until after the 10th week of pregnancy. During this time @entity26 concentration exerts a major influence over trophoblast activity and, @entity519 inducible factors are proposed to be one of many key regulators of first trimester trophoblast behaviour. We used a global gene expression microarray approach to identify signalling pathways and @entity519 -responsive genes of interest involved in invasion of the first trimester trophoblast cell line HTR8/SVneo under @entity519 conditions where @entity7738 was active. Additionally, first trimester placental samples from different gestational age groups were labelled with anti @entity7738 and @entity2032 to evaluate whether HIFs are differentially expressed and localised across two periods of placental development: (1) early first trimester characterised by @entity519 (6-8 weeks) and (2) late first trimester after initiation of maternal blood flow into the placenta (10-12 weeks). Invasion of HTR8/SVneo was assessed in real-time and was significantly increased in 1% compared with 5% and 21% @entity26 and did not differ between 5% and 21% @entity26 treatments. Eighty-eight genes were differentially expressed between cells cultured in 1% @entity26 (where @entity7738 protein was localised to the nucleus) and 5% @entity26 (where @entity7738 was mainly cytoplasmic). 65% of the genes were predicted to contain @entity7738 : @entity32299 transcription factor binding sites. While @entity2032 staining intensity in trophoblasts of late first trimester placenta was higher than early first trimester (+57%) the percentage of positively stained trophoblast nuclei did not differ between the two time points. There was no difference in the expression level of any of the @entity519 responsive genes of interest, @entity2301 , @entity71053 , @entity71054 , @entity8090 and @entity3334 between early and late first trimester placenta. While @entity7738 and its downstream targets are clearly induced in HTR8/SVneo during in vitro @entity519 conditions, it appears that @entity519 inducible factors and genes are not altered throughout the first 7-12 weeks of placental development, during which the onset of maternal blood flow to the intervillous space takes place.
