IGF-1Eb Isoform Immunoreactivity May Be Associated with Placental Dysfunction and Vascular Pathology in Fetal Growth Restriction (FGR)

Background: Fetal growth restriction (FGR) is associated with placental dysfunction and adverse perinatal outcomes. Although insulin-like growth factor-1 (IGF-1) signaling is important for placental and fetal development, the mRNA expression, immunopositivity and potential biological significance of specific IGF-1 isoforms in FGR remain incompletely characterized. This study investigated placental IGF-1Eb mRNA expression and immunopositivity in FGR pregnancies compared with appropriate-for-gestational-age (AGA) pregnancies. Methods: A total of 62 third-trimester human placentas were analyzed, including 47 from pregnancies complicated by FGR and 15 from pregnancies with AGA fetal growth. The mRNA expression of the IGF-1Eb isoform was assessed by reverse-transcription quantitative PCR in a subset of 28 fresh placental samples. IGF-1Eb protein immunoreactivity was assessed in paraffin-embedded tissue sections. Histopathological lesions were classified according to the Amsterdam criteria, and associations with clinical, demographic, and pathological parameters were evaluated using appropriate statistical analyses. Results: IGF-1Eb mRNA expression did not differ significantly between the FGR and AGA groups. In contrast, significant differences in IGF-1Eb immunoreactivity were observed in selected placental compartments. Moderate immunoreactivity in the perivillous syncytiotrophoblast was more frequent in FGR placentas and was associated with histological features of maternal vascular malperfusion, as well as with gestational age, neonatal birth weight, placental weight, maternal body mass index, and fetal sex. Increased IGF-1Eb immunopositivity was also observed in the endothelium of maternal decidual and fetal villous vessels in FGR placentas. No significant differences were observed in IGF-1Eb immunoreactivity in the extravillous trophoblast. Conclusions: In this observational study, placental IGF-1Eb protein immunoreactivity, but not mRNA expression, differed between FGR and AGA pregnancies in selected placental compartments. These findings indicate compartment-specific differences in IGF-1Eb protein immunoreactivity, associated with FGR and placental pathological features. However, the observational and cross-sectional design does not establish causality or a functional role for IGF-1Eb in placental dysfunction. Larger prospective studies incorporating functional validation are required to clarify the biological significance of these findings.