Ontogeny of growth-regulating genes in the placenta

Abstract

Background: Placental nutrient flow is the primary determinant of fetal growth. This key function of the placenta depends on several growth-promoting or -suppressing imprinted genes including Insulin-like growth factor [IGF] axis genes, which regulate nutrient transfer across the placenta. However whether changes in the placental expression of these genes parallel increased fetal growth observed in the second and third trimester remains unknown.

Objective: The aim of our study was to determine the ontogeny of key IGF axis genes and other growth regulating imprinted genes in the placenta and to characterize patterns of placental gene expression associated with intrauterine growth restriction (IUGR).

Study design: Real time RT-PCR analysis of 11 genes using specific probes were performed in the placental tissue collected at the time of delivery from 63 subjects with live birth pregnancies from 24 to 40 weeks gestation between 2009 -2010.

Results: We found that paternally expressed gene ZNF127 (p < 0.001) was upregulated whereas IGF1 (p = 0.001) and maternally expressed gene PHLDA2 (p = 0.001) were downregulated with advancing gestational age. ROC analysis revealed a significant change in the expression of the above genes early in the third trimester. When compared to age-matched appropriate for gestational age (AGA) infants, expression of PHLDA2 (p = 0.03) IGF2R (p < 0.05) was upregulated in IUGR infants. Maternal age was also a significant predictor for IUGR (p = 0.05).

Conclusion: We found increased placental expression of growth-promoting imprinted genes and decreased expression of growth-suppressive imprinted genes with advancing gestational age. These changes in placental gene expression could potentially explain accelerated fetal growth seen in the third trimester. Upregulation of maternally expressed imprinted genes in IUGR population supports the "parental conflict hypothesis".