Early Pregnancy Maternal Endocrine Insulin-Like Growth Factor I Programs the Placenta for Increased Functional Capacity throughout Gestation

Abstract

In early pregnancy, the concentrations of IGFs increase in maternal blood. Treatment of pregnant guinea pigs with IGFs in early to midpregnancy enhances placental glucose transport and fetal growth and viability near term. In the current study, we determined whether exogenous IGFs altered placental gene expression, transport, and nutrient partitioning during treatment, which may then persist. Guinea pigs were infused with IGF-I, IGF-II (both 1 mg/kg x d) or vehicle sc from d 20-35 of pregnancy and killed on d 35 (term is 70 d) after administration of [(3)H]methyl-D-glucose (MG) and [(14)C]amino-isobutyric acid (AIB). IGF-I increased placental and fetal weights (+15 and +17%, respectively) and MG and AIB uptake by the placenta (+42 and +68%, respectively) and fetus (+59 and +90%, respectively). IGF-I increased placental mRNA expression of the amino acid transporter gene Slc38a2 (+780%) and reduced that of Igf2 (-51%), without altering the glucose transporter Slc2a1 or Vegf and Igf1 genes. There were modest effects of IGF-I treatment on MG and AIB uptake by individual maternal tissues and no effect on plasma glucose, total amino acids, free fatty acids, triglycerides, and cholesterol concentrations. IGF-II treatment of the mother did not alter any maternal, fetal or placental parameter. In conclusion, exogenous IGF-I, but not IGF-II, in early pregnancy increases placental transport of MG and AIB, enhancing midgestational fetal nutrient uptake and growth. This suggests that early pregnancy rises in maternal circulating IGF-I play a major role in regulating placental growth and functional development and thus fetal growth throughout gestation.

Maternal Protein Restriction in the Rat Inhibits Placental Insulin, mTOR, and STAT3 Signaling and Down-Regulates Placental Amino Acid Transporters

“…Previous observations in the guinea pig demonstrate that maternal infusion of IGF-I from early pregnancy increases placental uptake and transfer of nutrients, in part by increasing placental transporter gene expression, enhancing placental and fetal growth by midpregnancy (64). Furthermore, IGF-I has been shown to stimulate system A amino acid transport in cultured human trophoblasts (30, 65) and insulin increases amino acid transport in trophoblasts mediated by system A (29, 30) and L (31).…”

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

“…In guinea pigs, early-pregnancy administration of IGF-1 increased the placental expression of glucose and amino acid transporter genes, increased placental uptake of glucose and amino acids, and increased placental and fetal growth by mid pregnancy (Sferruzzi-Perri et al, 2007). Consistent with these observations, mice treated with anti-IGF-1 antiserum showed reductions in amino acid uptake, placental weights, and fetal weights, while amino acid uptake and fetal weights were stimulated by an antiserum to the neutralizing IGFBP1 (Takeda and Iwashita, 1993).…”

Environmental regulation of placental phenotype: implications for fetal growth

“…However, IGF-I and IGF-II have different effects on placental phenotype. IGF-I stimulates expression of the SNAT and GLUT families of nutrient transporters in the guinea-pig placenta with both immediate and lasting effects on in vivo nutrient transfer by these systems (Sferruzzi-Perri et al 2007a, 2007b. Maternal IGF-II infusion induces morphological changes in the guinea-pig placenta with Lz expansion and an increased surface area for nutrient transfer, which are not seen with IGF-I treatment near term (Sferruzzi-Perri et al 2006).…”