Regulation of PI3K/Akt in preeclampsia: an examination of its pathological role and therapeutic potential.

Preeclampsia (PE) is a pregnancy-specific systemic condition characterized by the sudden emergence of elevated blood pressure, frequently accompanied by a significant presence of protein in the urine, or by the onset of high blood pressure alongside considerable damage to end organs, with or without the presence of proteinuria. The activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway within the placenta during PE may influence cell migration and angiogenesis, thereby helping to mitigate hypertension. Trophoblast cells, stimulated by human chorionic gonadotropin, migrate and invade through the PI3K/Akt pathway in vitro, involving downstream mediators such as matrix metalloproteinases (MMPs). Akt also regulates follicle development, embryo development, and granulosa cell survival, in addition to targeting the maturation and activation of immune and endothelial cells and affecting oxidative stress. These observations are indicative of the dysregulation of the PI3K/Akt signaling pathway having a role in PE pathophysiology via impaired angiogenesis, oxidative stress, inflammation, and trophoblast dysfunction. Hence, PI3K/Akt signaling modulation is a promising therapy to reverse placental dysfunction and related clinical symptoms of PE. Increased research on PI3K/AKT-targeted therapies has the potential for novel lines of clinical intervention resulting in an improvement of affected pregnancies. Herein, we discuss the pathological and therapeutic value of the PI3K/Akt pathways in PE by affecting oxidative stress, inflammation, and dysfunctions in angiogenesis, as well as adjusting trophoblastic cell growth and invasion.