Hormones as epigenetic signals in developmental programming

Abstract

In mammals, including man, epidemiological and experimental studies have shown that a range of environmental factors acting during critical periods of early development can alter adult phenotype. Hormones have an important role in these epigenetic modifications and can signal the type, severity and duration of the environmental cue to the developing feto-placental tissues. They affect development of these tissues both directly and indirectly by changes in placental phenotype. They act to alter gene expression, hence the protein abundance in a wide range of different tissues, which has functional consequences for many physiological systems both before and after birth. By producing an epigenome specific to the prevailing condition in utero, hormones act as epigenetic signals in developmental programming, with important implications for adult health and disease. This review examines the role of hormones as epigenetic signals by considering their responses to environmental cues, their effects on phenotypical development and the molecular mechanisms by which they programme feto-placental development, with particular emphasis on the glucocorticoids.

Hypothalamic expression of genes for appetite regulators and estrogen α, estrogen β and leptin receptors in obese dams and their fetuses

“…Although a strong correlation was not detected in the current study likely due to the limited sample size, a positive correlation between plasma leptin concentrations in the ewe and fetus in well-fed and under-nourished conditions during late pregnancy has been reported (Fowden and Forhead, 2009). It is not known whether this relationship is due to placental transfer of leptin or effects on the secretory capacity of leptin in the fetus.…”

The Effects of Glucocorticoids on Fetal and Placental Development

“…Additionally, glucocorticoids change the production and metabolism of hormones by the placenta such as prostaglandins, placental lactogen, leptin, corticotrophin-releasing hormone (CRH), estrogens, progesterone and other progestagens [63,64]. Glucocorticoids also alter the placental activity of various enzymes involved in the synthesis and inactivation of steroids and thyroid hormones such as 17,20-lyase, 17 -hydroxylase, aromatase, renin and endothelial nitric oxide synthase [63].…”

Endocrine Regulation of Feto-Placental Growth

“…However, compared to the fetus, relatively little is known about the endocrine regulation of placental development. The placenta itself produces hormones, including placental variants of pituitary hormones like growth hormone (GH) and prolactin, which may influence fetal growth directly or indirectly via maternal metabolic changes and altered partitioning of maternal resources to the fetus [7,8]. This review examines the role of hormones in regulating feto-placental growth with particular emphasis on the effects of insulin, glucocorticoids and the IGFs.…”

“…These hormones trigger key developmental events and control the cellular availability of nutrients for fetal growth more generally [3]. They also regulate rates of cell proliferation, apoptosis and differentiation in many fetal tissues [4]. Furthermore, hormones signal the availability of oxygen and nutrients to the developing fetal tissues and, thereby, match the fetal growth rate to the fetal nutrient supply [5].…”