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Maternal undernutrition during the first week after conception results in decreased expression of glucocorticoid receptor mRNA in the absence of GR exon 17 hypermethylation in the fetal pituitary in late gestation

Published online by Cambridge University Press:  30 August 2013

S. Zhang*
Affiliation:
Sansom Institute of Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Australia
O. Williams-Wyss
Affiliation:
Sansom Institute of Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Australia Discipline of Physiology, University of Adelaide, Adelaide, Australia
S. M. MacLaughlin
Affiliation:
Sansom Institute of Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Australia
S. K. Walker
Affiliation:
Turretfield Research Centre, South Australian Research and Development Institute, Rosedale, Australia
D. O. Kleemann
Affiliation:
Turretfield Research Centre, South Australian Research and Development Institute, Rosedale, Australia
C. M. Suter
Affiliation:
Victor Chang Cardiac Research Institute, Darlinghurst, Australia Faculty of Medicine, University of New South Wales, Kensington, Australia
J. L. Morrison
Affiliation:
Sansom Institute of Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Australia
L. Molloy
Affiliation:
Victor Chang Cardiac Research Institute, Darlinghurst, Australia
J. E. Cropley
Affiliation:
Victor Chang Cardiac Research Institute, Darlinghurst, Australia
C. T. Roberts
Affiliation:
Discipline of Obstetrics and Gynaecology, Robinson Institute, University of Adelaide, Adelaide, Australia
I. C. McMillen
Affiliation:
Sansom Institute of Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Australia
*
*Address for correspondence: S. Zhang, Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, P5-41, University of South Australia, City East, GPO 2471, Adelaide, SA 5001, Australia. (Email song.zhang@unisa.edu.au)

Abstract

Exposure to maternal undernutrition during the periconceptional period results in an earlier prepartum activation of the fetal hypothalamo–pituitary–adrenal (HPA) axis and altered stress responsiveness in the offspring. It is not known whether such changes are a consequence of exposure of the oocyte and/or the early embryo to maternal undernutrition in the periconceptional period. We have compared the effects of ‘periconceptional’ undernutrition (PCUN: maternal undernutrition imposed from at least 45 days before until 6 days after conception), and ‘early preimplantation’ undernutrition (PIUN: maternal undernutrition imposed for only 6 days after conception) on the expression of genes in the fetal anterior pituitary that regulate adrenal growth and steroidogenesis, proopiomelanorcortin (POMC), prohormone convertase 1 (PC1), 11β-hydroxysteroid dehydrogenase type 1 and 2 (11βHSD1 and 2) and the glucocorticoid receptor (GR) in fetal sheep at 136–138 days of gestation. Pituitary GR mRNA expression was significantly lower in the PCUN and PIUN groups in both singletons and twins compared with controls, although this suppression of GR expression was not associated with hypermethylation of the exon 17 region of the GR gene. In twin fetuses, the pituitary 11βHSD1 mRNA expression was significantly higher in the PIUN group compared with the PCUN but not the control group. Thus, exposure of the single or twin embryo to maternal undernutrition for only 1 week after conception is sufficient to cause a suppression of the pituitary GR expression in late gestation. These changes may contribute to the increased stress responsiveness of the HPA axis in the offspring after exposure to poor nutrition during the periconceptional period.

Type
Original Article
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2013 

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