Endoplasmic reticulum stress in the pathogenesis of early-onset pre-eclampsia

Recent data have provided molecular evidence of high levels of endoplasmic reticulum stress in non-laboured placentas from cases of early-onset pre-eclampsia. Endoplasmic reticulum stress is intricately linked to oxidative stress, and the two often share the same aetiology. In the case of pre-eclampsia this is likely to be placental malperfusion, secondary to deficient conversion of the spiral arteries. Endoplasmic reticulum stress activates a number of signalling pathways aimed at restoring homeostasis, but if these attempts fail then the apoptotic machinery may be activated. The potential consequences for placental development and function are numerous and diverse. Inhibition of protein synthesis results in lower levels of many kinases, growth factors and regulatory proteins involved in cell cycle control, and experiments in vitro reveal that endoplasmic reticulum stress slows cell proliferation. Chronic, low levels of stress during the second and third trimesters may therefore result in a growth restricted phenotype. Higher levels of endoplasmic reticulum stress lead to activation of pro-inflammatory pathways, a feature of pre-eclampsia that may contribute to maternal endothelial cell activation. These findings emphasise the complexity of cellular responses to stress, and the need to approach these in a holistic fashion when considering therapeutic interventions.