Downregulation of aromatase plays a dual role in preeclampsia

Abstract

Preeclampsia (PE) is a gestational disease, which seriously impairs maternal and infant health. However, the pathogenesis of PE remains unclear. The aromatase (CYP19A1) in placenta converts androgens from maternal and fetal adrenal glands to estrogen. Therefore, this change in the aromatase expression or function and the subsequent change of steroids in the placenta could be related to the pathophysiology of PE. In this study, we first analyzed the expression of CYP19A1 in clinical placental tissues as well as the level of sex hormones in corresponding serum samples. The results showed that the expression of aromatase in the placenta of PE patients was relatively low and accompanied by a sex hormone imbalance. Subsequently, animal experiments showed that ischemia and hypoxia lead to a low expression of CYP19A1, and that PE-like symptoms appear in pregnant mice following decreased or inhibited CYP19A1 expression. It was also found that, with the downregulation of CYP19A1 expression, the invasion and migration abilities of trophoblast cells were enhanced, which benefited placental implantation. However, alongside this, apoptosis and the inflammatory response were also increased, which was detrimental to placental development. Phosphoproteomic analyses revealed that the activation of the PI3K/AKT signaling pathway may play a key role in these processes. In conclusion, the downregulation of aromatase has a dual role in PE, among which the induction of the disease is the main role. Our study provides a potential novel method for the early prediction and treatment of PE.

Keywords: CYP19A1; PI3K-Akt; apoptosis; inflammatory response; preeclampsia.