Placental Neuropeptide Y (NPY) and NPY receptors expressions and serum NPY levels in preeclampsia

Abstract

© 2019 by the Society for Experimental Biology and Medicine. Neuropeptide Y (NPY) has been reported as a vasoconstrictive substance that might be associated with preeclampsia. NPY mediates different effects via its specific NPY receptors. NPY action via Y1 receptor (Y1R) and/or Y5 receptor (Y5R) induces vascular smooth muscle cells proliferation while it is implicated in angiogenesis via Y2 receptor (Y2R) and/or Y5R. The objectives of this study were to (1) compare placental NPY, Y1 receptor (Y1R), Y2 receptor (Y2R), and Y5 receptor (Y5R) expressions between normal (NP) and preeclamptic (PE) pregnancies to determine whether gene expression of different NPY receptors are altered in the PE condition; (2) compare maternal serum NPY levels between NP and PE subjects; and (3) determine correlations between placental gene expressions as well as serum NPY levels with maternal and neonatal clinical parameters. There were 22 subjects each in the NP (gestational age 37–42 weeks) and PE (gestational age ≥34 weeks) groups. Clinical parameters and serum NPY levels were measured before delivery. NPY expression and serum NPY levels were comparable between NP and PE subjects. Y1R, Y2R, and Y5R expressions were significantly lower in PE than NP subjects. In all and NP subjects, placental Y2R showed the highest expression, tended to be higher than Y5R, and was significantly higher than Y1R. In PE subjects, placental Y2R was comparable to Y5R and both Y2R and Y5R were significantly higher than Y1R. The NPY receptor expression ratio between the PE/NP groups showed that it was lowest for Y2R (0.27) compared to Y1R (0.42) and Y5R (0.40) suggestive of decreased Y2R expression in PE subjects. In summary, a decrease in placental Y2R mRNA might be associated with abnormalities of placental angiogenesis which probably contributes to the pathophysiology of preeclampsia. The roles of NPY receptors mediating placental vascularization need to be further investigated. Impact statement: Neuropeptide Y (NPY) has been reported as a vasoconstrictive substance which might be associated with preeclampsia. The novel findings of this study were that Y1R, Y2R, and Y5R expressions were significantly lower in the PE than the NP group. Moreover, the NPY receptor expression ratio between the PE/NP groups was lowest for Y2R (0.27) compared to Y1R (0.42) and Y5R (0.40) suggestive of a reduction of this receptor in the preeclampsia group. Our results suggested that decreased Y2R mRNA in the PE group might be associated with abnormalities of placental angiogenesis which probably contributes to the pathophysiology of preeclampsia.