Hostname: page-component-586b7cd67f-vdxz6 Total loading time: 0 Render date: 2024-11-23T11:54:27.079Z Has data issue: false hasContentIssue false
  • English
  • Français

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 ,
O. Williams-Wyss ,
S. M. MacLaughlin ,
S. K. Walker ,
D. O. Kleemann ,
C. M. Suter ,
J. L. Morrison ,
L. Molloy ,
J. E. Cropley  and
C. T. Roberts
...Show all authors
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 [email protected])
Get access Rights & Permissions [Opens in a new window]

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.

Keywords

fetal numberhypothalamo–pituitary–adrenal axismaternal undernutritionpreimplantation
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 4 , Issue 5 , October 2013 , pp. 391 - 401
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Liggins, GC. The role of cortisol in preparing the fetus for birth. Reprod Fertil Dev. 1994; 6, 141–150.Google Scholar
2.Whittle, WL, Patel, FA, Alfaidy, N, et al. Glucocorticoid regulation of human and ovine parturition: the relationship between fetal hypothalamic–pituitary–adrenal axis activation and intrauterine prostaglandin production. Biol Reprod. 2001; 64, 1019–1032.CrossRefGoogle ScholarPubMed
3.MacLaughlin, SM, McMillen, IC. Impact of periconceptional undernutrition on the development of the hypothalamo–pituitary–adrenal axis: does the timing of parturition start at conception? Curr Drug Targets. 2007; 8, 880–887.Google Scholar
4.Edwards, LJ, McMillen, IC. Impact of maternal undernutrition during the periconceptional period, fetal number, and fetal sex on the development of the hypothalamo–pituitary–adrenal axis in sheep during late gestation. Biol Reprod. 2002; 66, 1562–1569.Google Scholar
5.Gardner, DS, Jamall, E, Fletcher, AJW, Fowden, AL, Giussani, DA. Adrenocortical responsiveness is blunted in twin relative to singleton ovine fetuses. J Physiol. 2004; 557, 1021–1032.Google Scholar
6.Rumball, CWH, Oliver, MH, Thorstensen, EB, et al. Effects of twinning and periconceptional undernutrition on late-gestation hypothalamic–pituitary–adrenal axis function in ovine pregnancy. Endocrinology. 2008; 149, 1163–1172.Google Scholar
7.Bloomfield, FH, Oliver, MH, Hawkins, P, et al. Periconceptional undernutrition in sheep accelerates maturation of the fetal HPA axis in late gestation. Endocrinology. 2004; 145, 4278–4285.Google Scholar
8.Bloomfield, FH, Oliver, MH, Hawkins, P, et al. A periconceptional nutritional origin for non-infectious preterm birth. Science. 2003; 300, 561–562.Google Scholar
9.Hawkins, P, Hanson, MA, Matthews, SG. Maternal undernutrition in early gestation alters molecular regulation of the hypothalamic–pituitary–adrenal axis in the ovine fetus. J Neuroendocrinol. 2001; 13, 855–861.Google Scholar
10.Weaver, IC, Cervoni, N, Champagne, FA, et al. Epigenetic programming by maternal behaviour. Nat Neurosci. 2004; 7, 791–792.CrossRefGoogle Scholar
11.Oberlander, TF, Weinberg, J, Papsdorf, M, et al. Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics. 2008; 3, 97–106.CrossRefGoogle ScholarPubMed
12.McGowan, PO, Sasaki, A, D'Alessio, AC, et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci. 2009; 12, 342–348.Google Scholar
13.Stevens, A, Begum, G, Cook, A, et al. Epigenetic changes in the hypothalamic proopiomelanocortin and glucocorticoid receptor genes in the ovine fetus after periconceptional undernutrition. Endocrinology. 2010; 151, 3652–3664.CrossRefGoogle ScholarPubMed
14.McMillen, IC, Warnes, KE, Adams, MB, et al. Impact of restriction of placental and fetal growth on expression of 11{beta}-hydroxysteroid dehydrogenase type 1 and type 2 messenger ribonucleic acid in the liver, kidney, and adrenal of the sheep fetus. Endocrinology. 2000; 141, 539–543.CrossRefGoogle ScholarPubMed
15.Stewart, PM, Krozowski, ZS. 11 beta-Hydroxysteroid dehydrogenase. Vitam Horm. 1999; 57, 249–324.CrossRefGoogle Scholar
16.Tomlinson, JW, Stewart, PM. Cortisol metabolism and the role of 11[beta]-hydroxysteroid dehydrogenase. Best Pract Res Clin Endocrinol Metab. 2001; 15, 61–78.Google Scholar
17.Agricultural and Food Research Council. Energy and protein requirements of ruminants. An advisory manual prepared by the AFRC technical commitee on responses to nutrients, 1993. CAB International: Wallingford, UK.Google Scholar
18.Edwards, LJ, Simonetta, G, Owens, JA, Robinson, JS, McMillen, IC. Restriction of placental and fetal growth in sheep alters fetal blood pressure responses to angiotensin II and captopril. J Physiol. 1999; 515, 897–904.Google Scholar
19.MacLaughlin, SM, Walker, SK, Kleemann, DO, et al. Impact of periconceptional undernutrition on adrenal growth and adrenal insulin-like growth factor and steroidogenic enzyme expression in the sheep fetus during early pregnancy. Endocrinology. 2007; 148, 1911–1920.Google Scholar
20.Warnes, KE, McMillen, IC, Robinson, JS, Coulter, CL. Differential actions of metyrapone on the fatal pituitary-adrenal axis in the sheep fetus in late gestation. Biol Reprod. 2004; 71, 620–628.CrossRefGoogle Scholar
21.Myers, DA, Bell, PA, Hyatt, K, Mlynarczyk, M, Ducsay, CA. Long-term hypoxia enhances proopiomelanocortin processing in the near-term ovine fetus. Am J Physiol Regul Integr Comp Physiol. 2005; 288, R1178–R1184.Google Scholar
22.Gnanalingham, MG, Mostyn, A, Dandrea, J, et al. Ontogeny and nutritional programming of uncoupling protein-2 and glucocorticoid receptor mRNA in the ovine lung. J Physiol. 2005; 565, 159–169.CrossRefGoogle ScholarPubMed
23.Dodic, M, Hantzis, V, Duncan, J, et al. Programming effects of short prenatal exposure to cortisol. FASEB J. 2002; 16, 1017–1026.Google Scholar
24.Fletcher, CJ, Roberts, CT, Hartwich, KM, Walker, SK, McMillen, IC. Somatic cell nuclear transfer in the sheep induces placental defects that likely precede fetal demise. Reproduction. 2007; 133, 243–255.CrossRefGoogle ScholarPubMed
25.Muller, PY, Janovjak, H, Miserez, AR, Dobbie, Z. Processing of gene expression data generated by quantitative real-time RT-PCR. Biotechniques. 2002; 32, 1372–1379.Google Scholar
26.Bock, C, Reither, S, Mikeska, T, et al. BiQ analyzer: visualization and quality control for DNA methylation data from bisulfite sequencing. Bioinformatics. 2005; 21, 4067–4068.Google Scholar
27.McCormick, JA, Lyons, V, Jacobson, MD, et al. 5′-heterogeneity of glucocorticoid receptor messenger RNA is tissue specific: differential regulation of variant transcripts by early-life events. Mol Endocrinol. 2000; 14, 506–517.Google Scholar
28.Presul, E, Schmidt, S, Kofler, R, Helmberg, A. Identification, tissue expression, and glucocorticoid responsiveness of alternative first exons of the human glucocorticoid receptor. J Mol Endocrinol. 2007; 38, 79–90.CrossRefGoogle ScholarPubMed
29.Turner, JD, Muller, CP. Structure of the glucocorticoid receptor (NR3C1) gene 5′ untranslated region: identification, and tissue distribution of multiple new human exon 1. J Mol Endocrinol. 2005; 35, 283–292.Google Scholar
30.Turner, JD, Alt, SR, Cao, L, et al. Transcriptional control of the glucocorticoid receptor: CpG islands, epigenetics and more. Biochem Pharmacol. 2010; 80, 1860–1868.CrossRefGoogle ScholarPubMed
31.Neill, JD, Smith, PF, Luque, EH, et al. Detection and measurement of hormone secretion from individual pituitary cells. Recent Prog Horm Res. 1987; 43, 175–229.Google Scholar
32.Schwartz, J, Ash, P, Ford, V, et al. Secretion of adrenocorticotrophin (ACTH) and ACTH precursors in ovine anterior pituitary cells: actions of corticotrophin-releasing hormone, arginine vasopressin and glucocorticoids. J Endocrinol. 1994; 140, 189–195.Google Scholar
33.Butler, TG, Schwartz, J, McMillen, IC. Functional heterogeneity of corticotrophs in the anterior pituitary of the sheep fetus. J Physiol. 1999; 516, 907–913.CrossRefGoogle ScholarPubMed
34.Farrand, K, McMillen, IC, Tanaka, S, Schwartz, J. Subpopulations of corticotrophs in the sheep pituitary during late gestation: effects of development and placental restriction. Endocrinology. 2006; 147, 4762–4771.CrossRefGoogle ScholarPubMed
35.Ozolins, IZ, Antolovich, GC, Browne, CA, et al. Effect of adrenalectomy or long term cortisol or adrenocorticotropin (ACTH)-releasing factor infusion on the concentration and molecular weight distribution of ACTH in fetal sheep plasma. Endocrinology. 1991; 129, 1942–1950.Google Scholar
36.Ross, JT, Bennett, HPJ, James, S, McMillen, IC. Infusion of N-proopiomelanocortin-(1-77) increases adrenal weight and messenger ribonucleic acid levels of cytochrome P450 17{alpha}-hydroxylase in the sheep fetus during late gestation. Endocrinology. 2000; 141, 2153–2158.Google Scholar
37.McMillen, IC, Schwartz, J, Coulter, CL, Edwards, LJ. Early embryonic environment, the fetal pituitary-adrenal axis and the timing of parturition. Endocr Res. 2004; 30, 845–850.Google Scholar
38.Edwards, LJ, Bryce, AE, Coulter, CL, McMillen, IC. Maternal undernutrition throughout pregnancy increases adrenocorticotrophin receptor and steroidogenic acute regulatory protein gene expression in the adrenal gland of twin fetal sheep during late gestation. Mol Cell Endocrinol. 2002; 196, 1–10.Google Scholar
39.Edwards, LJ, Symonds, ME, Warnes, KE, et al. Responses of the fetal pituitary-adrenal axis to acute and chronic hypoglycemia during late gestation in the sheep. Endocrinology. 2001; 142, 1778–1785.CrossRefGoogle ScholarPubMed
40.Ozolins, I, Young, I, McMillen, I. Surgical disconnection of the hypothalamus from the fetal pituitary abolishes the corticotrophic response to intrauterine hypoglycemia or hypoxemia in the sheep during late gestation. Endocrinology. 1992; 130, 2438–2445.Google Scholar
41.Zhang, S, Rattanatray, L, MacLaughlin, SM, et al. Periconceptional undernutrition in normal and overweight ewes leads to increased adrenal growth and epigenetic changes in adrenal IGF2/H19 gene in offspring. FASEB J. 2010; 24, 2772–2782.Google Scholar