Placental abundances of IGF1, IGF2, IGFBP2, IGF2R and PPARα are associated with birth weight

Abstract Context The insulin/insulin-like growth factor (IGF) system is a key regulator of fetal growth and placental nutrient regulation. Objective To investigate associated gene and protein expressions of the insulin/IGF, adiponectin, and peroxisome proliferator-activated receptor (PPAR) pathways in placenta and cord blood from small-, appropriate-, or large-for-gestational age (SGA, AGA, LGA) infants and corresponding first-trimester maternal blood. Methods A total of 60 SGA, 109 AGA, and 55 LGA term infants (birth weight z-scores <-2, –2 to +2, and >2, respectively) were included. Placental mRNA expression of 22 genes was analyzed using RT‒qPCR. Immunohistochemistry (IHC) was used to determine the protein localization and abundance of five differentially expressed genes in 78 representative placental samples. Cord blood and maternal blood concentrations of related proteins were analyzed by ELISA. Results Placental gene expression of IGF1, IGF2, IGBP2, IGF2R, and PPARA was significantly lower in the SGA group. A moderate correlation in expression levels was observed among differentially expressed genes, except for IGF2R.In the SGA group, IHC staining for IGF1, IGF2, IGF2R, and PPARα was weaker, while IGFBP2 staining was stronger. In the cord blood, the IGF1 and IGF2 concentrations increased successively from the SGA group to the LGA group, whereas the IGFBP2 concentration decreased successively. No differences in maternal blood were observed between the groups. Conclusion Placental IGF1, IGF2, and PPARα signaling are positively associated with birth weight, whereas that of IGFBP2 is negatively associated, possibly reflecting a shared upstream regulation by nutrition. Conversely, placental IGF2R signaling may aid in normalizing abnormal fetal growth.