Abstract
<jats:p>Background: Idiopathic intrauterine growth restriction (IUGR) is strongly associated with placental dysfunction, impaired spiral uterine artery remodeling, and adverse perinatal outcomes. Although insulin-like growth factor-1 (IGF-1) signaling is essential for placental and fetal development, the role of specific IGF-1 isoforms remains unclear. This study investigated placental IGF-1Eb expression in idiopathic IUGR and its potential as a biomarker of placental dysfunction. Methods: A total of 62 third-trimester human placentas were analyzed, including 47 from pregnancies complicated by idiopathic intrauterine growth restriction (IUGR) and 15 from pregnancies with appropriate-for-gestational-age (AGA) fetal growth, which served as the control group. The mRNA expression levels of the IGF-1Eb isoform were assessed by reverse transcription quantitative PCR in a subset of 28 fresh placental samples. The immunoexpression of IGF-1Eb protein was assessed in paraffin-embedded tissue sections. Histopathological lesions were classified according to the Amsterdam criteria, and correlations with clinical, demographic and pathological parameters were assessed using appropriate statistical analyses. Results: The mRNA expression of the IGF-1Eb isoform in placentas did not differ significantly between the IUGR and AGA groups. In contrast, immunohistochemical analysis revealed statistically significant differences in IGF-1Eb protein expression. The protein localization was cytoplasmic, perimembranous and occasionally nuclear, expressed in the perivillous and extravillous trophoblast, and the endothelium of fetal and maternal vessels. Moderate IGF-1Eb immunoexpression in the perivillous syncytiotrophoblast was observed significantly more frequently in IUGR placentas compared with the AGA group and was associated with histological changes of maternal vascular malperfusion, and with clinical parameters, including gestational age, neonatal birth weight, placental weight, maternal body mass index, and fetal sex. Furthermore, a significant increase in IGF-1Eb immunopositivity was observed in the endothelium of maternal decidual and fetal villous vessels in IUGR placentas. In contrast, no statistically significant differences were recorded in the scores or intensity of IGF-1Eb immunoexpression in the extravillous trophoblast between the two groups. Conclusions: Although total IGF-1Eb mRNA levels remained unchanged, increased protein immunoexpression was associated with idiopathic IUGR in distinct parts of the placenta. In association with histological changes of maternal vascular malperfusion, these findings suggest that IGF-1Eb may serve as a potential marker of placental dysfunction in IUGR pregnancies.</jats:p>