Fetal endocrinology and development - manipulation and adaptation to long-term nutritional and environmental challenges

This article reviews the fetal endocrine system in sheep, a species that ha s a long gestation and primarily produces a singleton fetus. Attention is f ocused on information that is applicable to humans. The endocrinology of me tabolic homeostasis in sheep fetuses is well adapted to respond to a range of metabolic challenges, including placental restriction and maternal under nutrition. A small placenta results in hypoxaemia, hypoglycaemia, reduced a bundance of anabolic hormones, and fetal growth restriction. Fetuses with r estricted growth are characterized by tissue-specific reductions in hormone receptor mRNA, for example mRNA for the long form of prolactin receptor is reduced in adipose tissue. In contrast, the adipose tissue of fetuses with accelerated growth, stimulated by increasing maternal nutrition in the sec ond half of gestation, has more protein for the long form of the prolactin receptor and more uncoupling protein 1, by which large amounts of heat are generated at birth. Maternal undernutrition in early gestation, coinciding with the period of rapid placental growth, initially restricts placental gr owth, but when mothers are fed to requirements, a longer fetus results with a disproportionately large placenta. This nutritional manipulation replica tes, in part, epidemiological findings from the Dutch famine of 1944-1945, for which the offspring are at increased risk of adult obesity.