Appropriate partitioning of nutrients between the mother and conceptus is a major determinant of pregnancy success, with placental transfer playing a key role. Insulin-like growth factors (IGFs) increase in the maternal circulation during early pregnancy and are predictive of fetal and placental growth. We have previously shown in the guinea pig that increasing maternal IGF abundance in early to midpregnancy enhances fetal growth and viability near term. We now show that this treatment promotes placental transport to the fetus, fetal substrate utilization, and nutrient partitioning near term. Pregnant guinea pigs were infused with IGF-I, IGF-II (both 1 mg.kg-1.day-1) or vehicle subcutaneously from days 20-38 of pregnancy (term=69 days). Tissue uptake and placental transfer of the nonmetabolizable radio analogs [3H]methyl-D-glucose (MG) and [14C]aminoisobutyric acid (AIB) in vivo was measured on day 62. Early pregnancy exposure to elevated maternal IGF-I increased placental MG uptake by>70% (P=0.004), whereas each IGF increased fetal plasma MG concentrations by 40-50% (P<0.012). Both IGFs increased fetal tissue MG uptake (P<0.048), whereas IGF-I also increased AIB uptake by visceral organs (P=0.046). In the mother, earlier exposure to either IGF increased AIB uptake by visceral organs (P<0.014), whereas IGF-I also enhanced uptake of AIB by muscle (P=0.044) and MG uptake by visceral organs (P=0.016) and muscle (P=0.046). In conclusion, exogenous maternal IGFs in early pregnancy sustainedly increase maternal substrate utilization, placental transport of MG to the fetus, and fetal utilization of substrates near term. This was consistent with the previously observed increase in fetal growth and survival following IGF treatment.

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.

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A 44-year-old nulliparous woman was transferred to a tertiary obstetric hospital for investigation of acute onset abdominal pain. She was at gestation of 32 weeks and 2 days with a history of previous laparoscopic fundal myomectomy. An initial bedside ultrasound demonstrated oligohydramnios. Following an episode of increased pain early the following morning, a formal ultrasound diagnosed a uterine rupture with the fetal arm extending through a uterine rent. An uncomplicated classical caesarean section was performed and the neonate was delivered in good condition but with a bruised and oedematous right arm. The neonate was transferred to the Special Care Nursery for neonatal care. The patient had an uncomplicated postoperative course and was discharged home three days following delivery. This is an unusual presentation of uterine rupture following myomectomy where the fetal arm had protruded through the uterine wall.

The data obtained in the current study suggest the potential for alternate roles for the induction of the RAS after IGF treatment. IGF1 and 2 treatments increase the activation of prorenin to renin in the placenta, possibly due to increased protease activity. In addition, IGF2 treatment in early pregnancy may enhance the maternal adaptation to pregnancy through stimulation of renin in the kidney. The sustained effects on placental differentiation and function after IGF2 treatment suggest therapeutic potential for exogenous administration of IGFs in improving pregnancy outcomes.