Maternal iron status during pregnancy compared with neonatal iron status better predicts placental iron transporter expression in humans

Abstract

The placenta richly expresses nonheme and heme Fe transport proteins. To address the impact of maternal and neonatal Fe status and hepcidin on the regulation of these proteins, mRNA expression and protein abundance of nonheme and heme Fe transport proteins were evaluated in placental tissue from 154 adolescents. Regression analyses found maternal Fe status was significantly associated with multiple placental nonheme and heme transporters, whereas neonatal Fe status was related to only 3 heme transporters. Across statistical analyses, maternal Fe status was consistently associated with the placental nonheme Fe importer transferrin receptor 1 (TfR1). Protein abundance of TfR1 was related to midgestation maternal serum ferritin (SF) (β = -0.32; P = 0.005) and serum TfR (β = 0.25; P = 0.024). Protein abundance of the heme importer, proton-coupled folate transporter, was related to neonatal SF (β = 0.30; P = 0.016) and serum TfR (β = -0.46; P < 0.0001). Neonatal SF was also related to mRNA expression of the heme exporter feline leukemia virus subgroup C receptor 1 (β = -0.30; P = 0.004). In summary, maternal Fe insufficiency during pregnancy predicts increased expression of the placental nonheme Fe transporter TfR1. Associations between placental heme Fe transporters and neonatal Fe status require further study.-Best, C. M., Pressman, E. K., Cao, C., Cooper, E., Guillet, R., Yost, O. L., Galati, J., Kent, T. R., O'Brien, K. O. Maternal iron status during pregnancy compared with neonatal iron status better predicts placental iron transporter expression in humans.

Keywords: TfR1 hepcidin; adolescents; anemia; heme.

Figure 1.

A) Correlations between measures of mRNA expression of placental nonheme and heme Fe transport proteins. B) Correlations between measures of protein abundance. Correlations were statistically significant at P < 0.05, adjusted for false discovery rate. These correlations remained statistically significant when tested in multiple linear regression models that adjusted for variables that can impact the functional status of the placenta, including placental weight, birth weight, gestational age (wk), maternal gynecologic age at conception (yr), maternal pregnancy weight gain, maternal prepregnancy body mass index, and maternal race. FPN, ferroportin; ZYK, zyklopen.

Figure 2.

Direct and mediating effects of neonatal Fe status on placental expression of 2 heme transporters: Results from 3 structural equation models. A) Model 1: maternal SF at midgestation had an independent effect (1) on umbilical cord SF (β = 0.46; P < 0.001). Cord SF had an independent effect (2) (β = 0.30; P = 0.016) and mediated the indirect effect (3) of maternal SF (β = 0.14; P = 0.04) on the heme importer PCFT protein abundance. Maternal SF had no direct effect (4) on PCFT protein. B) Model 2: maternal sTfR at midgestation had an independent effect (1) on umbilical cord sTfR (β = 0.37; P < 0.001). Cord sTfR had an independent effect (2) (β = −0.46; P < 0.0001) and mediated the indirect effect (3) of maternal sTfR (β = −0.17; P = 0.006) on the heme importer PCFT protein abundance. Maternal sTfR had no direct effect (4) on PCFT protein. C) Model 3: maternal SF at midgestation had an independent effect (1) on umbilical cord SF (β = 0.47; P < 0.001). Cord SF had an independent effect (2) (β = −0.30; P = 0.004) and mediated the indirect effect (3) of maternal SF (β = −0.14; P = 0.02) on the heme exporter FLVCR1 mRNA expression. Maternal SF had no direct effect (4) on FLVCR1 mRNA. *P < 0.05; **P < 0.01; *** P < 0.001.