The dysfunctional placenta epigenome: causes and consequences

The placenta is a fetal-maternal endocrine organ responsible for ensuring proper fetal development throughout pregnancy. Adverse insults to the intrauterine environment often lead to expression level changes in placental genes, many of which are epigenetically regulated by DNA methylation, histone modifications and ncRNA interference. These epigenetic alterations may cause placental dysfunction, resulting in offspring of low birthweight owing to adverse pregnancy complications such as intrauterine growth restriction. Numerous epidemiological studies have shown a strong correlation between low birthweight and increased risk of developing metabolic diseases and neurological imbalances in adulthood, and in subsequent generations, indicating that epigenetic regulation of gene expression can be propagated stably with long-term effects on health. This article provides an overview of the various environmental factors capable of inducing detrimental changes to the placental epigenome, as well as the corresponding mechanisms that prime the offspring for onset of disease later in life.