Environmental epigenetics: a role in endocrine disease?

Abstract

Endocrine disrupting chemicals that are structurally similar to steroid or amine hormones have the potential to mimic endocrine endpoints at the receptor level. However, more recently, epigenetic-induced alteration in gene expression has emerged as an alternative way in which environmental compounds may exert endocrine effects. We review concepts related to environmental epigenetics and relevance for endocrinology through three broad examples: 1) effect of early-life nutritional exposures on future obesity and insulin resistance, 2) effect of lifetime environmental exposures such as ionizing radiation on endocrine cancer risk, and 3) potential for compounds previously classified as endocrine disrupting to additionally or alternatively exert effects through epigenetic mechanisms. The field of environmental epigenetics is still nascent, and additional studies are needed to confirm and reinforce data derived from animal models and preliminary human studies. Current evidence suggests that environmental exposures may significantly impact expression of endocrine-related genes and thereby affect clinical endocrine outcomes.

Figure 1

Many endocrine disrupting chemicals such as DES have structural similarity to steroid hormones such as estrogen.

Figure 2

Exposures that occur preconception, in utero, in early life, and in adult life may result in epigenetic dysregulation.

Figure 3

There are multiple potential causal pathways through which an environmental exposure may lead to epigenetic modifications which may, in turn, impact clinical outcomes. Additional human studies that extend over the entire causal pathway are needed to establish cause-and-effect relationships between exposures and outcomes.