Identification of placental genes linked to selective intrauterine growth restriction (IUGR) in dichorionic twin pregnancies: gene expression profiling study

A linkage of dichorionic (DC) twin pregnancies with selective intrauterine growth restriction (IUGR) to alterations in placental gene expression is unclear. The aim of the study was to identify placental genes related to hypoxia, adipogenesis and human growth which may contribute to IUGR development. The study group (IUGR/AGA) comprised dichorionic (DC) twin pregnancies, where the weight of the twins differed by>15%; in addition, one twin was small for gestational age (<10th percentile-SGA) (IUGR) while the other was appropriate for gestational age (>10th percentile-AGA). In the control group (AGA/AGA), both fetuses were AGA and their weights differed by<15%. In the first step (selection), placental expression of 260 genes was analysed by commercial PCR profiler array or qPCR primer assay between six pairs of IUGR/AGA twins. In the second stage (verification), the expression of 20 genes with fold change (FC)>1.5 selected from the first stage was investigated for 75 DC pregnancies: 23 IUGR/AGA vs. 52 AGA/AGA. The expression of Angiopoetin 2, Leptin and Kruppel-like factor 4 was significantly higher, and Glis Family Zinc Finger 3 was lower, in placentas of SGA fetuses (FC=3.3; 4.4; 1.6; and -1.8, respectively; p<0.05). The dysregulation of gene expression related to angiogenesis and growth factors in placentas of twins born from IUGR/AGA pregnancies suggest that these alternations might represent biological fetal adaptation to the uteral condition. Moreover, DC twin pregnancies may be a good model to identify the differences in placental gene expression between SGA and AGA fetuses.