The IGF axis in baboon pregnancy: placental and systemic responses to feeding 70% global ad libitum diet

Abstract

Information on the influence of poor maternal nutrition on the regulation of responses to pregnancy, placental and fetal growth and development is critical to a better understanding of pregnancy physiology and pathophysiology. We determined normal changes and effects of controlled and monitored moderate nutrient restriction (NR) (global nutrient intake reduced to 70% of food consumed by mothers feeding ad libitum from 0.16 to 0.5 of gestation) in the baboon, on important hematological, biochemical, and hormonal indices of fetal growth and placental function. Serum IGF-I:IGFBP-3 ratio was lower in pregnant than control non-pregnant baboons feeding ad libitum. Serum concentrations of total and free IGF-I were decreased in NR mothers compared with controls (p<0.05). The decrease in fetal IGF-I did not reach significance (p=0.057). Serum IGF-I: IGFBP-3 ratio was decreased by NR in both mothers and fetuses. Maternal serum IGF-II was unchanged by NR. Placental IGF-I mRNA and protein abundance were similarly reduced whereas IGF-II mRNA increased in placental tissue of NR compared to control mothers. Systemic (maternal) and local (placental) IGFBP-1 and IGFBP-3 mRNA and protein abundance were unchanged by NR. Type 1 IGF receptor protein in the syncytiotrophoblast increased in NR. Type 2 IGF receptor protein was present in the stem villi core, and decreased after NR. We conclude that moderate NR in this important non-human primate model significantly disrupts the maternal and placental IGF-IGFBP axis and influences placental expression of this key system at the gene and protein level. Changes observed appear to be directed toward preserving placental growth.

Fig. 1

A, Serum measurements in adult female baboons when non-parous (NP, n = 12), fed ad libitum (control, n = 5) at 90 dG, and when fed 70% of control (from 30 to 90 days gestation (dG)) and at 90 dG (NR, n = 6). B, Fetal serum measurements at 90 days gestation (dG) in baboons fed ad libitum (control, n = 5) and 70% of control (NR) at 90 dG from 30 to 90 dG (NR, n = 6) animals. Values are mean ± SE; SE is too small to show for the IGF-I/IGFBP-3 ratio (A). *p < 0.05 vs. control (unpaired t-test).

Fig. 2

IGF-I gene (in situ hybridization, first row) and protein (immunohistochemistry, second row) expression in placentae from control (A and D; n = 6) and 30% maternal NR (B and E; n = 6) groups at 90 dG. Inset (D), Negative control. Quantification for all animals (C and F). IGF-II expression (in situ hybridization, third row) and protein location (immunohistochemistry, fourth row) in placentae from control (G and J; n = 6) and 30% maternal NR (H and K; n = 6) groups at 90 dG. Quantification for all animals (I and L). *p < 0.05 vs. control. Magnification 20×.

Fig. 3

IGFBP-1 expression (in situ hybridization, first row) and protein location (immunohistochemistry, second row) in placentae from control (A and D; n = 6) and 30% maternal NR (B and E; n = 6) groups at 90 dG. Quantification for all animals (C and F). IGFBP-3 expression (in situ hybridization, third row) and protein location (immunohistochemistry, fourth row) in placentae from control (G and J; n = 6) and 30% maternal NR (H and K; n = 6) groups at 90 dG. Quantification for all animals (I and L). *p < 0.05 vs. control. Magnification 20× (A, B, G, H, J, K) and 40×(D and E).

Fig. 4

IGF1R (first row) and IGF2R (second row) immunohistochemistry in placentae from control (n = 6) and 30% maternal NR (n = 6) groups at 90 dG. Quan-tification for all animals (C and F). *p < 0.05 vs. control. Magnification 20×.