Insulin-like growth factor-1 receptor expression in the placentae of diabetic and normal pregnancies☆

Abstract 

Background

Septal hypertrophic cardiomyopathy (sHCM) is a characteristic anomaly of the infant of diabetic mother (IDM). Insulin-like growth factor-1 (IGF-1) has been identified as a mediator of tissue overgrowth and we have previously shown that maternal IGF-1 levels were significantly elevated among neonates with asymmetrical sHCM. IGF-1 does not cross the placenta; it exerts physiologic action through binding to the IGF-1 receptor (IGF-1R). Localisation and expression of IGF-1R in term diabetic pregnancies are largely unclear. We have studied IGF-1R in the placentae of diabetic and normal pregnancies and this receptor expression in association with neonates with sHCM.

Methods

IGF-1R localization and expression in the placentae of six diabetic pregnancies associated with neonatal sHCM were compared with six each of randomly selected diabetic and normal pregnancies without neonatal sHCM by immunohistochemistry. The staining for IGF-1R in the deciduas, cytotrophoblasts, syncytiotrophoblasts and villous endothelium for these 18 samples were assessed and scored by two pathologists who were blinded to the respective diagnoses.

Results

Placental IGF-1R staining was negative in the villous endothelium for all three groups. IGF-1R staining was present in deciduas, cytotrophoblasts and syncytiotrophoblasts but the staining was weaker in the entire group of infants with sHCM compared to those without sHCM.

Conclusions

IGF-1R is localized in all cell types of the placenta except in villous endothelium. Weaker placental IGF-1R staining in the placentae of diabetic pregnancies associated with sHCM suggests reduced expression of IGF-1R. This may be a down-regulatory response to elevated maternal IGF with neonatal sHCM outcome.

Abbreviations: DNA, deoxyribonucleic acid, GDM, gestational diabetes mellitus, H&E, haematoxylin and eosin, HBA1c, glycosylated hemoglobin, IDM, infant of diabetic mother, IGF, insulin-like growth factor, IGF-1R, insulin-like growth factor 1 receptor, IGT, impaired glucose tolerance, IVS, interventricular septum, sHCM, septal hypertrophic cardiomyopathy, TBS, Tris-buffered saline, WHO, World Health Organization