1.2.1. Placental Ischemia

Poor placentation resulting from the insufficient EVT invasion and reduced uterine blood flow leading to placental ischemia have been proposed to be one of the leading causes of PE. Specifically, placental ischemia is associated with an imbalance of immune function and chronic inflammation similar to autoimmune diseases [15–17]. This immune imbalance creates a state of chronically uncontrolled inflammation due to an increase in the production of pro-inflammatory factors and the abnormal activation of immune cells and production of cytokines, whilst decreasing the abundance of regulatory immune cells and cytokines [18,19]. These alterations lead to progressive pathophysiological changes including an enhanced production of reactive oxygen species [20], increased oxidative and endoplasmic reticulum stress, endothelin-1 expression, production of potent pro-inflammatory mediators [21], anti-angiogenic factors at the implantation site, and the production of autoantibodies such as angiotensin-II type I receptor (AT1-AA) [22], thus culminating in the development of hypertension during pregnancy. Therefore, insight into how different components of the innate immune system and

inflammatory cytokines are regulated and contribute to the progression of development of PE will be useful in developing targeted therapies that are necessary to improve pregnancy outcomes.
