The Role of Placental Homeobox Genes in Human Fetal Growth Restriction

Padma Murthi,Shaun Patrick Brennecke,Gayathri Rajaraman,Bill Kalionis

doi:10.1155/2011/548171

Padma Murthi, Shaun Patrick Brennecke + Show 2 more

Open Access

https://doi.org/10.1155/2011/548171

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Abstract

Fetal growth restriction (FGR) is an adverse pregnancy outcome associated with significant perinatal and paediatric morbidity and mortality, and an increased risk of chronic disease later in adult life. One of the key causes of adverse pregnancy outcome is fetal growth restriction (FGR). While a number of maternal, fetal, and environmental factors are known causes of FGR, the majority of FGR cases remain idiopathic. These idiopathic FGR pregnancies are frequently associated with placental insufficiency, possibly as a result of placental maldevelopment. Understanding the molecular mechanisms of abnormal placental development in idiopathic FGR is, therefore, of increasing importance. Here, we review our understanding of transcriptional control of normal placental development and abnormal placental development associated with human idiopathic FGR. We also assess the potential for understanding transcriptional control as a means for revealing new molecular targets for the detection, diagnosis, and clinical management of idiopathic FGR.

Highlights

We review our understanding of transcriptional control of normal placental development and abnormal placental development associated with human idiopathic Fetal growth restriction (FGR)
Previous studies from our laboratory have demonstrated the expression of homeobox genes HLX, DLX3, DLX4, MSX2, and GAX in placental endothelial cells, and we showed that novel placental homeobox genes, such asTLX1, TLX2, TGIF, HEX, PHOX1, MEIS2, HOXB7, and LIM6 were expressed in placental endothelial cells [84]
By using short-interference RNA (siRNA)-mediated inactivation of HLX approach, we investigated the mechanisms by which HLX mediates extravillous trophoblast function in normal and FGR-affected placentae

Summary

Introduction

FGR is commonly defined as a birth weight of less than the 10th percentile for gestation, together with evidence of fetal health compromise such as oligohydramnios and asymmetric fetal growth involving an increased head to abdominal circumference ratio. Evidence of such underlying pathology allows clinicians to discriminate between FGR and healthy small for gestation age (SGA) babies that are otherwise normal. Clinical features of idiopathic FGR pregnancies include abnormal umbilical artery Doppler velocimetry [12], oligohydramnios [13], and asymmetric fetal growth [14]. A consequence of altered placental function in idiopathic FGR is reduced transfer of oxygen, nutrients, and growth factors to the fetus, which restricts fetal growth [21]. In many animal model systems, early developmental stages are controlled at the level of transcription factors

Transcriptional Control of Placental Development

Homeobox Genes

Findings

Conclusions and Future Directions