Human Placenta Expresses α₂-Adrenergic Receptors and May Be Implicated in Pathogenesis of Preeclampsia and Fetal...

α₂-Adrenergic receptors (α₂ARs) are G-protein-coupled receptors involved in catecholamine signaling by extracellular regulated protein kinase 1 and 2 (ERK1/2) pathways. We examined placental expression and function of α₂AR subtypes in women with severe preeclampsia (sPE) with and without intrauterine growth restriction (IUGR). Placental biopsies were analyzed from 52 women with i) sPE (n = 8); ii) sPE + IUGR (n = 9); iii) idiopathic IUGR (n = 8); iv) idiopathic preterm birth (n = 16); and v) healthy term controls (n = 11). Expression of α₂AR subtypes (α_2A, α_2B, α_2C) and phospho-ERK1/2 (receptor activation marker) was investigated by immunohistochemistry and/or quantitative real-time RT-PCR. The effects of α_2CAR knockdown on syncytialization (syncytin-1 and -2) and β-human chorionic gonadotropin secretion were examined in BeWo cells stimulated with forskolin. The effects of α₂AR agonist UK 14,304 and specific α_2CAR antagonist were tested, using a trophoblast migration assay. All three α₂ARs were expressed and functionally active in human placenta with site-specific localization. Highest α_2BAR and α_2CAR mRNA expression was identified in sPE + IUGR. α_2CAR knockdown increased expression of syncytin-1 and -2 but decreased secretion of β-human chorionic gonadotropin. UK 14,304 impaired trophoblast migration. The observed α₂AR expression pattern suggests different function for each subtype. α_2CAR modulates trophoblast syncytialization and migration and may carry pathogenic role in sPE + IUGR.