Expression of the IGF‑1Ea isoform in human placentas from third trimester normal and idiopathic intrauterine growth restriction singleton pregnancies: Correlations with clinical and histopathological parameters.

Intrauterine growth restriction (IUGR) is the second most common obstetric complication after preterm labor. Appropriate trophoblast differentiation and placental structure, growth and function are key for the maintenance of pregnancy and normal fetal growth, development and survival. Extravillous trophoblast cell proliferation, migration and invasion are regulated by molecules produced by the fetomaternal interface, including autocrine factors produced by the trophoblast, such as insulin‑like growth factor (IGF)‑1. The aim of the present study was to investigate expression patterns of IGF‑1Ea isoform in IUGR placenta compared with appropriate for gestational age (AGA) pregnancies. Placental frozen tissues were collected from 13 AGA and 15 IUGR third trimester pregnancies for detection of IGF‑1Ea mRNA expression using reverse transcription‑quantitative PCR. Formalin‑fixed paraffin‑embedded samples from 15 AGA and 47 IUGR pregnancies were analyzed immunohistochemically for the identification and localization of the IGF‑1Ea peptide and comparison of clinical and histopathological parameters. To the best of our knowledge, the present study is the first to show IGF‑1Ea expression in third trimester human placenta. The results indicated that similar IGF‑1Ea mRNA expression levels were present in placental specimens from both groups. Cytoplasmic IGF‑1Ea expression was localized in the perivillous syncytiotrophoblast, extravillous trophoblast and endothelium of the villous and decidual vessels in both groups. No significant difference in the scores and intensity of IGF‑1Ea expression in perivillous syncytiotrophoblasts were noted in the IUGR vs. AGA pregnancies. Most IUGR cases showed negative IGF‑1Ea expression in the extravillous trophoblast, whereas AGA pregnancies showed predominantly positive immunostaining. A sex‑specific expression pattern was noted in the extravillous trophoblast, with negative IGF‑1Ea expression in the placentas of female IUGR cases. Additionally, positive immunostaining for IGF‑1Ea peptide in fetal villous and maternal decidual vessels, was more frequently observed in the IUGR group compared with AGA. In conclusion, no difference in total IGF‑1Ea mRNA placental expression was observed between IUGR and AGA pregnancies, likely due to heterogeneity of histological structures expressing this isoform. Negative IGF‑1Ea immunohistological expression in the extravillous trophoblast from IUGR placentas, associated with histological changes of maternal malperfusion, may reflect the involvement of this isoform in defective placentation. The presence of IGF‑1Ea peptide in the endothelium of the villous vessels in IUGR placentas may indicate a reactive autocrine regulation to compensate for malperfused villi in IUGR pregnancy by regulating angiogenesis and vasodilation. The observed sex differences in IGF‑1Ea expression between IUGR and AGA placentas may indicate interactions between sex hormones and selective IGF‑1 binding proteins in regulating IGF‑1Ea synthesis; however, this requires further elucidation.