Submitted on October 29, 2007
Accepted on February 11, 2008
Placental restriction of fetal growth decreases IGF1 and leptin mRNA expression in the perirenal adipose tissue of late gestation fetal sheep
Jaime A Duffield1, Tony Vuocolo2, Ross L Tellam3, Bernard SJ Yuen4, Beverly S Muhlhausler5, and I Caroline McMillen6*
1 School of Molecular and Biomedical Sciences, Discipline of Physiology, University of Adelaide, Adelaide, South Australia, Australia; Sansom Institute, Research Centre for the Early Origins of Adult Health, School of Pharmacy and Medical Science, University of South Australia, Adelaide, South Australia, Australia
2 Livestock Industries, CSIRO, Brisbane, Queensland, Australia
3 Livestock Industries, CSIRO, St Lucia, Queensland, Australia
4 School of Molecular and Biomedical Sciences, Discipline of Physiology, University of Adelaide, Adelaide, South Australia, Australia
5 Sansom Institute, Research Centre for the Early Origins of Adult Health, School of Pharmacy and Medical Science, University of South Australia, Adelaide, South Australia, Australia; Discipline of Physiology, School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, South Australia, Australia
6 Sansom Institute, Research Centre for the Early Origins of Adult Health, School of Pharmacy and Medical Science, University of South Australia, Adelaide, South Australia, Australia; , Australia
* To whom correspondence should be addressed. E-mail: caroline.mcmillen{at}unisa.edu.au.
Placental restriction (PR) of fetal growth results in a low birth weight and an increased visceral fat mass in postnatal life. We have investigated whether PR alters expression of genes which regulate adipogenesis (IGF1, IGF1R, IGF2, IGF2R, PPAR
, RXR
), adipocyte metabolism (LPL, G3PDH, GAPDH) and adipokine signalling (leptin, adiponectin) in visceral adipose tissue before birth. PR was induced by removal of the majority of endometrial caruncles in non pregnant ewes prior to mating. Fetal blood samples were collected from 116d gestation and perirenal visceral adipose tissue (PAT) collected from PR and control fetuses at 145d. PAT gene expression was measured by qRT-PCR. PR fetuses had a lower weight (PR 2.90 ± 0.32 kg; Control, 5.12 ± 0.24 kg; P<0.0001), mean gestational arterial PO2 (P<0.0001), plasma glucose (P<0.01) and insulin concentrations (P<0.02), than Controls. The expression of IGF1 mRNA in PAT was lower in the PR fetuses (PR 0.332 ± 0.063; Control 0.741 ± 0.083; P<0.01). Leptin mRNA expression in PAT was also lower in PR fetuses (PR 0.077 ± 0.009; Control, 0.115 ± 0.013; P<0.05), although there was no difference in the expression of other adipokine or adipogenic genes in PAT between PR and control fetuses. Thus restriction of placental and hence fetal substrate supply results in decreased IGF1 and leptin expression in fetal visceral adipose tissue which may alter the functional development of the perirenal fat depot and contribute to altered leptin signalling in the growth restricted new born and the subsequent emergence of an increased visceral adiposity.
