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.

Influence of moderate maternal nutrition restriction on the fetal baboon metabolome at 0.5 and 0.9 gestation

“…The total amounts of fetal plasma lysoPCa, PCaa, PCae, and SM increased significantly from 0.5G to 0.9G in fetal plasma of the MNR group, but not in the CTR group (Table 2). in the MNR than CTR fetuses [21]. This increase was shown to be due to an enhanced activity of PEPCK which results from decreased methylation of the gene's promoter [13].…”

Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates

“…Moreover, HNF4α can functionally bind to the promoters of up to 12% of all hepatic genes (89), suggesting that HNF4α has broad activities and may contribute to a much larger regulatory network of essential metabolic processes in the liver. Although the increases in gluconeogenic gene expression at G130 were relatively small compared with expression in adult liver, in transgenic mice engineered to overexpress hepatic PCK1 at birth, a 2-fold increase was sufficient to induce hepatic glucose production, insulin resistance, and impaired glucose tolerance in adults (69), suggesting that relatively small increases during development could prove to be significant in the evolution of diabetes. These data would be greatly strengthened by measures of increased hepatic glucose production; however, this was not technically feasible in the NHP fetus.…”

“…It has been demonstrated in numerous models, including rodents, sheep, and NHPs, that manipulation of the maternal diet or hormone environment can affect the development of metabolic systems in the offspring (15-18, 22-24, 64). Using NHP models, Nathanielsz and colleagues have demonstrated a broad range of metabolic and developmental defects in the offspring of mothers with nutritional restriction (65)(66)(67)(68)(69)(70). These broad effects are surprising, because the animals are nutritionally restricted by only 30%.…”

Maternal‐placental insulin‐like growth factor (IGF) signaling and its importance to normal embryo‐fetal development

“…Baseline data have been published on maternal and fetal IGF levels in later pregnancy (Tarantal and Gargosky, 1995). Otherwise, the only perturbations of the system that have been evaluated are nutrient restriction in the first trimester, demonstrating altered mRNA and protein expression of placental IGF-1, IGF-2, and IGF-1R (Li et al, 2007) or placental morphological changes .…”