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Am J Physiol Regul Integr Comp Physiol 292: R1934-R1942, 2007. First published January 4, 2007; doi:10.1152/ajpregu.00802.2006
0363-6119/07 $8.00
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DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Effects of maternal parity and late gestational nutrition on mRNA abundance for growth factors in the liver of postnatal sheep

Melanie A. Hyatt,1,2 Helen Budge,1 David Walker,2 Terence Stephenson,1 and Michael E. Symonds1

1Centre for Reproduction and Early Life, Institute of Clinical Research, and 2Children's Brain Tumour Research Centre, The University of Nottingham, Nottingham, United Kingdom

Submitted 15 November 2006 ; accepted in final form 3 January 2007

The liver is a major metabolic and endocrine organ in growing neonates, but the extent to which its hormone receptor (R) sensitivity is potentially determined by maternal parity and the mother's nutritional environment is unknown. This was therefore investigated by sampling livers from postnatal sheep born to nulliparous or multiparous mothers. Offspring were sampled 1 or 30 days after birth from mothers consuming either 100 or 50% [i.e., nutrient-restricted (NR) group] of total metabolizable energy requirements from 110 days gestation to term (~147 days). Regardless of maternal diet, offspring of nulliparous mothers were lighter at birth and had smaller livers. By 1 mo of age, they exhibited catch-up growth, an adaptation not seen when mothers were NR, but they retained their lighter livers. At both sampling ages, livers from offspring born to nulliparous mothers exhibited increased mRNA abundance for growth hormone (GH) receptor, IGF-IR, plus hepatocyte growth factor (HGF); and at day 1 only IGF-I, but not IGF-IIR mRNA was decreased. In addition, mRNA for IGF-II, the HGFR, c-Met, and Bax were persistently reduced in these offspring. Effects of parity were largely unaffected by maternal nutrient restriction. Maternal parity therefore has a substantial effect on liver size during postnatal development and its receptor population that is not dependent on maternal diet. First-born offspring appear to exhibit a resetting of the endocrine control of hepatic growth within the HGF and GH-IGF axis, which could have later consequences after their growth has caught up.

birth weight; insulin-like growth factor; hepatocyte growth factor; Bax



Address for reprint requests and other correspondence: M. E. Symonds; Academic Division of Child Health, School of Human Development, Univ. Hospital, Nottingham NG7 2UH, United Kingdom (e-mail: Michael.Symonds{at}nottingham.ac.uk)







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