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Type: Journal article
Title: Periconceptional undernutrition in normal and overweight ewes leads to increased adrenal growth and epigenetic changes in adrenal IGF2/H19 gene in offspring
Author: Zhang, S.
Rattanatray, L.
MacLaughlin, S.
Cropley, J.
Suter, C.
Molloy, L.
Kleemann, D.
Walker, S.
Muhlhausler, B.
Morrison, J.
McMillen, I.
Citation: FASEB Journal, 2010; 24(8):2772-2782
Publisher: Federation Amer Soc Exp Biol
Issue Date: 2010
ISSN: 0892-6638
Statement of
Song Zhang, Leewen Rattanatray, Severence M. MacLaughlin, Jennifer E. Cropley, Catherine M. Suter, Laura Molloy, Dave Kleemann, Simon K. Walker, Beverly S. Muhlhausler, Janna L. Morrison, and I. Caroline McMillen
Abstract: Adverse conditions in early life result in increased activation of the hypothalamo-pituitaryadrenal axis and in stress responsiveness in offspring. We have developed a model in which “donor” ewes are either normally nourished or overnourished prior to a period of dietary restriction, before transfer of the embryo at 6 –7 d after conception to a ewe of normal weight and nutritional history. A moderate restriction of energy intake during the periconceptional period in both normal weight and overweight ewes resulted in increased adrenal mass in male and female lambs and an increased cortisol response to stress in female lambs. The increase in adrenal weight in lambs exposed to periconceptional undernutrition was associated with a decrease in the adrenal mRNA expression of IGF2 and decreased methylation in the proximal CTCF-binding site in the differentially methylated region of the IGF2/H19 gene. Thus, weight loss in both normal and overweight mothers during the periconceptional period results in epigenetic modification of IGF2 in the adrenal gland, adrenal overgrowth, and increased vulnerability to stress in offspring. Determining the appropriate approach to weight loss in the periconceptional period may therefore be important in overweight or obese women seeking to become pregnant.
Keywords: Fetus; embryo; hypothalamo-pituitary axis; cortisol; DNA methylation
Rights: Copyright status unknown
RMID: 0020101686
DOI: 10.1096/fj.09-154294
Appears in Collections:Molecular and Biomedical Science publications

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