Embryo number and periconceptional undernutrition in the sheep have differential effects on adrenal epigenotype, growth, and development

作者：Williams Wyss Olivia; Zhang Song; MacLaughlin Severence M; Kleemann David; Walker Simon K; Suter Catherine M; Cropley Jennifer E; Morrison Janna L; Roberts Claire T; McMillen I Caroline^*

来源：American Journal of Physiology - Endocrinology And Metabolism, 2014, 307(2): E141-E150.

DOI：10.1152/ajpendo.00051.2012

• adrenal
• epigenetic
• periconceptional
• twin
• fetus

Exposure to poor maternal nutrition around the time of conception results in an early prepartum activation of the fetal pituitary-adrenal axis and in increased adrenal growth and stress response after birth associated with epigenetic changes in a differentially methylated region (DMR) of adrenal IGF2/H19. We have determined the effects of maternal undernutrition during the periconceptional period (PCUN: 70% of control intake from 60 days before until 6 days after conception) and early preimplantation period (PIUN: 70% of control intake for 6 days after conception) on fetal plasma ACTH and cortisol concentrations and fetal adrenal ACTHR, StAR, 3 beta HSD, CYP11B, CYP17, TGF beta 1, IGF1, IGF1R, IGF2, and IGF2R mRNA expression and the methylation level of sites within the DMRs of IGF2/H19 and IGF2R in the adrenal of twin and singleton fetuses at 136-138 days gestation. Being a twin resulted in a delayed prepartum increase in fetal ACTH and in a lower cortisol response to CRH in the control but not PCUN and PIUN groups. PCUN, but not PIUN, resulted in an increase in adrenal weight and CYP17 expression in singletons, a decrease in adrenal IGF2 expression in singletons, and an increase in adrenal IGF2R expression in both twins and singletons. IGF2/H19 and IGF2R DMR methylation levels and ACTHR expression were lower in the twin adrenal. Thus, exposure of the oocyte and embryo to maternal undernutrition or to the environment of a twin pregnancy have differential effects on epigenetic and other factors that regulate fetal adrenal growth and IGF2 and IGF2R expression.

• 出版日期2014-7-15