Downstream targets of the homeobox gene DLX3 are differentially expressed in the placentae of pregnancies affected by human idiopathic fetal growth restriction

Amy Chui, Bill Kalionis, Mohamed Abumaree, Melanie Cocquebert, Thierry Fournier, Daniele Evain-Brion, Shaun P. Brennecke, Padma Murthi

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Abstract

Human idiopathic fetal growth restriction (FGR) is associated with placental insufficiency. Previously, we reported that the expression of homeobox gene Distal-less 3 (DLX3) is increased in idiopathic FGR placentae and is a regulator of villous trophoblast differentiation. Here, we identify the downstream targets of DLX3 in trophoblast-derived cell lines. We modelled the high levels of DLX3 in FGR using an over-expression plasmid construct and complemented this using short-interference RNA (siRNA) for inactivation in cultured cells. Using a real-time PCR-based gene profiling, candidate target genes of DLX3 over-expression and inactivation were identified as regulators of trophoblast differentiation; GATA2 and PPARγ. The expression of GATA2 and PPARγ were further assessed in placental tissues and showed increased mRNA and protein levels in FGR-affected tissues compared with gestation-matched controls. We conclude that DLX3 orchestrates the expression of multiple regulators of trophoblast differentiation and that expression of these regulatory genes is abnormal in FGR.

Original languageEnglish
Pages (from-to)75-83
Number of pages9
JournalMolecular and Cellular Endocrinology
Volume377
Issue number1-2
DOIs
Publication statusPublished - 5 Sep 2013
Externally publishedYes

Keywords

  • Fetal growth
  • Homeobox genes
  • Human placenta
  • Trophoblast

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