Gene expression patterns of insulin-like growth factor 1, 2 (IGF-1, IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) in human placenta from preterm deliveries: influence of additional factors

Abstract

Introduction: In this study, we compared human placental gene expression patterns of IGF from pregnancies that ended with preterm delivery versus full term pregnancies as controls. We also assessed differences in clinical characteristics in the two groups. Materials and Methods: We used real-time PCR to assess gene expression patterns of IGF in human placental samples from 104 preterm and 140 full term pregnancies (control group) at the time of delivery. Clinical data were collected from our computerized database. Results: Pre-gestational Body Mass Index (BMI) was not significantly different in the two groups. In the preterm delivery group, the proportion of smokers was 26.9%, significantly higher than in the control group (7.1%, p<0.05). Preterm delivery began with premature rupture of membranes in 70.2% and spontaneous uterine activity in 29.8%. History of preterm delivery was present in 14.4% in the preterm delivery group compared to only 4.3% of the control group (p<0.05). In preterm delivery, placental samples showed an underexpression of the IGF-1 gene compared to controls. In samples derived from pregnancies with male fetal gender an overexpression of both the IGF-2 and the IGFBP-3 genes were observed. Gestational age did not influence gene expression patterns within the preterm delivery group. Discussion: Among environmental factors influencing preterm delivery, smoking was the most significant in our study. In the majority of cases, preterm delivery was induced by intrauterine infection leading to accumulation of inflammatory substances reducing the activity of the IGF system. This mechanism may also play a role in the development of neurological sequelae as well as a decreased tolerance to fetal distress. The overexpression of the IGF-2 gene observed in the placenta with male fetal gender can be explained by its physiological role in the development of male phenotype. Positive maternal history of preterm delivery appears to be a risk factor for subsequent preterm deliveries.