The Apelinergic System in Pregnancy

Abstract

The apelinergic system is a highly conserved pleiotropic system. It comprises the apelin receptor apelin peptide jejunum (APJ) and its two peptide ligands, Elabela/Toddler (ELA) and apelin, which have different spatiotemporal localizations. This system has been implicated in the regulation of the adipoinsular axis, in cardiovascular and central nervous systems, in carcinogenesis, and in pregnancy in humans. During pregnancy, the apelinergic system is essential for embryo cardiogenesis and vasculogenesis and for placental development and function. It may also play a role in the initiation of labor. The apelinergic system seems to be involved in the development of placenta-related pregnancy complications, such as preeclampsia (PE) and intrauterine growth restriction, but an improvement in PE-like symptoms and birth weight has been described in murine models after the exogenous administration of apelin or ELA. Although the expression of ELA, apelin, and APJ is altered in human PE placenta, data related to their circulating levels are inconsistent. This article reviews current knowledge about the roles of the apelinergic system in pregnancy and its pathophysiological roles in placenta-related complications in pregnancy. We also discuss the challenges in translating the actors of the apelinergic system into a marker or target for therapeutic interventions in obstetrics.

Keywords: APJ; Elabela; apelin; placenta; preeclampsia; pregnancy.

Figure 1

Apelinergic system expression and roles in placenta. ELA: Elabela; EVT: extravillous trophoblast.

Figure 2

Activation of different signaling pathways through ELA (framed in green), apelin (framed in green), or both (framed in cyan) in the binding of APJ in human trophoblast [59,68,69]. ELA: Elabela; APJ: apelin peptide jejunum; AMPK: adenosine monophosphate-activated protein kinase; ERK1/2: extracellular signal-activated kinase 1/2; PKA: protein kinase A; PI3K: phosphatidylinositol 3-kinases.