Nutritional manipulation between early to mid-gestation: effects on uncoupling protein-2, glucocorticoid sensitivity, IGF-I receptor and cell proliferation but not apoptosis in the ovine placenta

Abstract

In sheep, modest maternal nutrient restriction (NR) over the period of rapid placental growth restricts placentome growth and results in offspring in which glucocorticoid action is enhanced. Therefore, this study investigated the placental effects of early to mid-gestational NR on glucocorticoid receptor (GR), 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2), uncoupling protein-2 (UCP2), and IGF type-I receptor (IGF-IR) mRNA abundance together with cell proliferation and apoptosis as determined histologically, and the mitochondrial proteins voltage-dependent anion channel and cytochrome c that are involved in apoptosis. Placenta was sampled at 80 and 140 days gestation (dGA; term ~147 dGA). NR was imposed between 28 and 80 days gestation when control and nutrient-restricted groups consumed 150 or 60% respectively of their total metabolizable energy requirements. All mothers were then fed to requirements up to term. Total fetal placentome weights were decreased by NR at 80 dGA but were heavier at 140 dGA following 60 days of nutritional rehabilitation. GR and UCP2 mRNA abundance increased whilst 11betaHSD2 mRNA decreased with gestational age. NR persistently up-regulated GR and UCP2 mRNA abundance. 11betaHSD2 mRNA was reduced by NR at 80 dGA but increased near to term. IGF-IRmRNA abundance was only decreased at 80 dGA. Placental apoptosis and mitochondrial protein abundance were unaffected by NR, whereas cell proliferation was markedly reduced. In conclusion, placental UCP2 and local glucocorticoid action are affected by the gestational nutritional status and may result in the offspring showing enhanced glucocorticoid sensitivity, thereby predisposing them to disease in later life.