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Impact of Periconceptional Undernutrition on Adrenal Growth and Adrenal Insulin-Like Growth Factor and Steroidogenic Enzyme Expression in the Sheep Fetus during Early Pregnancy

Disciplines of Physiology (S.M.M., D.N.T., C.L.C., I.C.M.) and Biochemistry (J.P.S.), School of Molecular and Biomedical Science, University of Adelaide, Adelaide 5005; South Australian Research and Development Institute (S.K.W., D.O.K.), Turretfield Research Centre, Rosedale 5350; and Sansom Institute (S.M.M., D.N.T., S.G., I.C.M.), School of Pharmacy and Medical Sciences, University of South Australia, Adelaide 5000, South Australia, Australia

Address all correspondence and requests for reprints to: Professor I. C. McMillen, Head, Early Origins of Adult Health Research Group, The Sansom Research Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5000, Australia. E-mail: caroline.mcmillen{at}unisa.edu.au.

Periconceptional undernutrition (PCUN) results in an earlier prepartum activation of the pituitary-adrenal axis in twin compared with singleton fetuses. We have tested the hypotheses that the functional development of the fetal sheep adrenal is delayed in twins compared with singletons in early gestation and that PCUN accelerates adrenal growth and increases the expression of intraadrenal IGF-I and -II and cytochrome P450 17-hydroxylase (CYP17) as early as 55 d gestation. We have investigated the effect of PCUN in the ewe (restricted at 70% of control allowance, n = 21; control, n = 24) from at least 45 d before mating until d 7 after mating on maternal cortisol and progesterone concentrations, fetal adrenal weight, adrenal IGF-I, IGF-I receptor (IGF-IR), IGF-II, IGF-IIR, and CYP17 mRNA expression and placental 11ß-hydroxysteroid dehydrogenase-1 and -2 mRNA and protein expression at d 53–56 pregnancy. The relative weight of the fetal adrenal and adrenal IGF-I, IGF-IR, IGF-II, IGF-IIR, and CYP17 mRNA expression were lower in twin compared with singleton fetuses. In singleton fetuses of PCUN ewes, there was a loss of the relationship between adrenal IGF-II/IGF-IIR expression and either adrenal weight or CYP17 mRNA, which was present in controls. Similarly in twin fetuses, PCUN resulted in the loss of the relationships between adrenal weight and IGF-I expression and between adrenal CYP17 and IGF-II expression, which were present in controls. Our findings suggest that differences in the timing of the prepartum activation of the fetal adrenal in twins and singletons have their origins in early gestation and highlight the importance of the interaction between the periconceptional environment and embryo number in setting the growth trajectory of the fetal adrenal.

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