Periconceptional undernutrition in normal and overweight ewes leads to increased adrenal growth and epigenetic changes in adrenal IGF2/H19 gene in offspring.
Adverse conditions in early life result in increased activation of the hypothalamo-pituitary-adrenal 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.
Zhang
Song
S
Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
Rattanatray
Leewen
L
MacLaughlin
Severence M
SM
Cropley
Jennifer E
JE
Suter
Catherine M
CM
Molloy
Laura
L
Kleemann
Dave
D
Walker
Simon K
SK
Muhlhausler
Beverly S
BS
Morrison
Janna L
JL
McMillen
I Caroline
IC
D000311:Adrenal Glands / Q000254:growth & development*; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D044127:Epigenesis, Genetic; D005260:Female; D005306:Fertilization; D006854:Hydrocortisone / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008297:Male; D044342:Malnutrition / Q000503:physiopathology*; D009035:Mothers; D050177:Overweight; D011247:Pregnancy; D012333:RNA, Messenger; D012756:Sheep; D015431:Weight Loss
D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II; D006854:Hydrocortisone