Relevance of genomic imprinting in intrauterine human growth expression of CDKN1C, H19, IGF2, KCNQ1 and PHLDA2 imprinted genes.

PURPOSE: To study the relationship of imprinted gene expression (CDKN1C, H19, IGF2, KCNQ1 and PHLDA2) with human fetal growth.

METHODS: RNA was extracted from fetuses with intrauterine growth restriction (IUGR) and from the controls without growth restriction. The gene expression pattern of CDKN1C, H19, IGF2, KCNQ1 and PHLDA2 genes was evaluated using RT-PCR. MS-MLPA was also performed to assess the IC1 and IC2 DNA methylation status on chromosome 11p15.5.

RESULTS: The samples were divided according to their tissue type in placental or fetal tissue. Within each group, IUGR cases and controls were compared. In the IUGR cases, in both fetal and placental tissue groups IGF2 was observed to be down regulated. In another approach, the samples were divided in IUGR and control groups and for each of them placental and fetal tissue was compared. Within the IUGR group up regulation of CDKN1C, KCNQ1, and PHLDA2 was determined in placental samples. IUGR group presented a statistically lower methylation status in both IC1 and in IC2. Regarding differences between fetal and placental samples within this group, methylation status of placental samples was statistically significant down regulated in the imprinting center 1 (IC1).

CONCLUSIONS: Genomic imprinting is a phenomenon that plays an important role in fetal and placental development. This study emphasizes the importance of imprinted genes during pregnancy. Differences between tissues could reflect different mechanisms, either compensatory or adverse, that should be investigated in more detail.