Differential regulation of igf1 and igf1r mRNA levels in the two hepatic lobes following intrauterine growth restriction and its treatment with intra-amniotic insulin-like growth factor-1 in ovine fetuses
Revati A. Darp A , Hendrina A. de Boo A , Hui Hui Phua A , Mark H. Oliver A , José G. B. Derraik A , Jane E. Harding A and Frank H. Bloomfield A BA Liggins Institute, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
B Corresponding author. Email: f.bloomfield@auckland.ac.nz
Reproduction, Fertility and Development 22(8) 1188-1197 https://doi.org/10.1071/RD09292
Submitted: 1 December 2009 Accepted: 11 May 2010 Published: 1 October 2010
Abstract
Intrauterine growth restriction (IUGR) has life-long health implications, yet there is no effective prenatal treatment. Daily intra-amniotic administration of insulin-like growth factor (IGF)-1 to IUGR fetal sheep improves fetal gut maturation but suppresses hepatic igf1 gene expression. Fetal hepatic blood supply is regulated, in part, by shunting of oxygen- and nutrient-rich umbilical venous blood through the ductus venosus, with the left hepatic lobe predominantly supplied by umbilical venous blood and the right hepatic lobe predominantly supplied by the portal circulation. We hypothesised that: (1) once-weekly intra-amniotic IGF-1 treatment of IUGR would be effective in promoting gut maturation; and (2) IUGR and its treatment with intra-amniotic IGF-1 would differentially affect igf1 and igf1r mRNA expression in the two hepatic lobes. IUGR fetuses received 360 µg IGF-1 or saline intra-amniotically once weekly from 110 until 131 days gestation. Treatment of IUGR fetuses with IGF-1 reversed impaired gut growth. In unembolised, untreated control fetuses, igf1 mRNA levels were 19% lower in the right hepatic lobe than in the left; in IUGR fetuses, igf1 and igf1r mRNA levels were sixfold higher in the right lobe. IGF-1 treatment reduced igf1 and igf1r mRNA levels in both lobes compared with IUGR fetuses. Thus, weekly intra-amniotic IGF-1 treatment, a clinically feasible approach, reverses the impaired gut development seen in IUGR. Furthermore, igf1 and igf1r mRNA levels are differentially expressed in the two hepatic lobes and relative expression in the two lobes is altered by both IUGR and intra-amniotic IGF-1 treatment.
Additional keywords: amniotic fluid, fetal therapy, gastrointestinal tract, somatotrophic axis.
Acknowledgements
The authors thank members of the Fetal and Neonatal Physiology Group at the Liggins Institute (University of Auckland) for their assistance with this work. The authors gratefully acknowledge financial support from the Health Research Council of New Zealand.
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