Review: Placental homeobox genes and their role in regulating human fetal growth

The regulation of fetal growth is multifactorial and complex. Normal fetal growth is determined by the genetically predetermined growth potential and further modulated by maternal, fetal, placental, and environmental factors. The placenta provides critical transport functions between the maternal and fetal circulations during intrauterine development. Formation of this interface is controlled by several growth factors, cytokines and transcription factors including homeobox genes. This review summarizes our current knowledge regarding homeobox genes in the human placenta and their differential expression and functions in human idiopathic fetal growth restriction (FGR). The review also describes the research strategies that were used for the identification of homeobox genes, their expression in FGR, functional role and target genes of homeobox genes in the trophoblasts and the hormonal regulators of homeobox gene expression in vitro. A better understanding of molecular pathways driven by placental homeobox genes and further elucidation of signaling pathways underlying the hormone-mediated homeobox gene developmental programs may offer novel strategies of targeted therapy for improving feto-placental growth in idiopathic FGR pregnancies.