The human placenta expresses all of the genes of the prorenin/prorenin receptor (PRR) - angiotensin system (PRR-RAS) required to produce angiotensin II (Ang II), as well as both Ang II receptor subtypes. Ang II, acting via the AT1 receptor, stimulates cytotrophoblast proliferation, migration, invasion and angiogenesis.
The first trimester is a critical window for placental development, during which placental development occurs in a low oxygen environment that is known to stimulate blood vessel development and cell growth through the upregulation of growth factors. The placental PRR-RAS is also known to be upregulated during early gestation and is able to stimulate these growth factors.
We propose that appropriate activation of the placental RAS during this period ensures sufficient oxygen and nutrient supplies to the fetus throughout pregnancy. On the other hand, insufficient RAS activation could be associated with sub-optimal placental development and as a result increased likelihood of adverse pregnancy events, such as preterm birth and preeclampsia.
Our recent research has demonstrated that the low oxygen environment is responsible for the upregulation of some components of the placental PRR-RAS but that activation of the placental PRR-RAS is not driven by the low oxygen tension alone; it is more likely that a combination of low oxygen, cAMP and miRNAs regulates the placental RAS.
I will discuss our recent research findings on the regulation of the placental PRR-RAS by low oxygen, miRNAs and cAMP and how the placental PRR-RAS acts in co-ordination with these to regulate placental growth and angiogenesis. This presentation will highlight the importance of the placental PRR-RAS in physiological and pathological placental development.