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The relationship of Insulin-like growth factor-2 IGF2 expression in Chorion Villus Samples (CVS) from fetal growth restriction (FGR)) and normal pregnancies

Presented at the Neonatal Society 2012 Summer Meeting (programme).

Aggarwal R1,2, Demetriou C1, Thomas A1, Nicolaides K2,3, Moore G1, Peebles D2

1 Clinical and Molecular Genetics, Institute of Child Health, London
2 University College London Hospital, London. cKing’s College Hospital, London

Background: Fetal growth restriction (FGR) is a major cause of stillbirth, intrauterine hypoxia, acidosis and death. Fetal growth relies on an effective nutrient supply from the mother to the fetus via the placenta, which is influenced by a complex inter-relationship of environment and genetics. Of particular interest is genomic imprinting which is an epigenetic phenomenon leading to the silencing of one of the parental gene copies resulting in mono-allelic expression in a parent-of origin manner. Its evolution is probably best explained by the ‘conflict hypothesis’ which suggests that paternally expressed imprinted genes promote fetal growth ensuring inheritance of the paternal genome to successive generations, while maternally expressed imprinted genes limit growth in order for the mother to survive and reproduce again (1). Several imprinted genes have been implicated in human syndromes and disorders including insulin-like growth factor (IGF-2) which is a potent embryonic growth factor associated with Beckwith-Wiedemann syndrome, Silver-Russell Syndrome, hepatocellular carcinoma and Wilm’s tumour (2). We postulated that IGF2 expression analysis of chorionic villus samples of normal and growth restricted pregnancies would show a difference when compared with birth centile.

Methods: 100 chorionic villus samples were obtained at 12-14 weeks gestation originating from singleton pregnancies resulting in live deliveries of which 50 were below 5th centile and the remainder between 6th and 80th birth centile. RNA was extracted from the tissue, complementary DNA (cDNA) was synthesised using reverse transcription for the Real-Time quantitative PCR (RTqPCR). Relative expression of IGF2 was determined by ratio of their expression to that of a housekeeping gene for each sample. Statistical analysis was conducted to correlate IGF2 expression with anthropometric measurements of the fetus as well as maternal clinical data.

Results: Whilst there was a trend to higher IGF2 expression in the growth restricted group, this was not significant using an unpaired t-test (t=-1.871, df= 74, p=0.065). However, standard multiple regression (correcting for gestational age and sex of the fetus and maternal BMI) in the control group exhibited a positive relationship between IGF2 expression and birth weight. A similar relationship was not observed within the IUGR group.

Conclusion: IGF2 expression in first trimester villi correlates with birth weight within a normal range. Although there was a suggestion that expression might also be higher in fetuses that went on to become growth restricted, this was not significant; however, as numbers are small and IUGR is a very heterogeneous condition, the study needs to be replicated with larger numbers for this association to be verified. This is one of the first studies to use CVS to quantify IGF2 expression and attempt to correlate with fetal growth restriction.

Corresponding author:

1. Moore, T. and Haig, D. (1991). Genomic imprinting in mammalian development: a parental tug-of-war. Trends Genet. 7, 45-49.
2. Abu-Amero SN, Monk, D, Apostolidou S, Stanier P, Moore GE (2006), Imprinted genes and their role in human fetal growth. Cytogenet Genome Res 113:262-270

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