As the adipokine leptin regulates development, we investigated if growth restriction due to uteroplacental insufficiency alters leptin concentrations in maternal and offspring plasma, and amniotic fluid. As leptin can increase urinary albumin/protein and plasma concentrations of pro-fibrotic cytokine TGFb1, we characterised these in maternal urine and plasma. Our hypothesis was that in response to growth restriction, plasma leptin concentrations in offspring born small would be reduced compared to controls. Further that maternal plasma leptin, TGFb1, and urinary protein and albumin would be increased in growth restricted pregnancies.
Female WKY rats were mated and at day 18 of pregnancy (E18) underwent sham surgery or bilateral ligation of the uterine vessels to induce uteroplacental insufficiency. At E20, offspring were sacrificed and maternal urine and plasma and offspring plasma and amniotic fluid collected. Plasma leptin and TGFb1 concentrations were quantified using a leptin and TGFb1 ELISAs, and urinary protein and albumin determined using a BCA assay, and rat albumin ELISA, respectively.
In restricted males and females, there was a significant reduction in fetal body weight at E20 compared to controls. In mothers with a restricted pregnancy, there was no change in plasma concentrations of leptin or TGFb1, and no change in total urinary protein. However, there was a significant increase in urinary albumin in mothers with a restricted pregnancy compared to control, which is indicative of early renal dysfunction. Amniotic fluid leptin concentrations were not significantly different in restricted offspring compared to control, however plasma leptin concentrations were significantly reduced in restricted male and female fetuses compared to controls.
Thus, we have demonstrated that growth restriction induced by uteroplacental insufficiency reduces fetal leptin concentrations, which may delay or impair organogenesis. Further, increased maternal albuminuria suggests that compromised placental function in the restricted pregnancy may increase circulating factors essential for normal renal function.