Pre-B cell colony enhancing factor (PBEF/NAMPT/Visfatin) and vascular endothelial growth factor (VEGF) cooperate to increase the permeability of?the?human placental amnion

Abstract

Fluid efflux across the region of the amnion overlying the placenta is an essential component of the intramembranous absorption pathway that maintains amniotic fluid volume homeostasis. Dysregulation of this pathway may result in adverse pregnancy outcomes, however the factors controlling amnion permeability are unknown. Here, we report a novel mechanism that increases placental amnion permeability. Pre-B Cell Colony Enhancing Factor (PBEF) is a stress-responsive cytokine expressed by the human amnion, and is known to induce Vascular Endothelial Growth Factor (VEGF) production by other cell types. Interestingly, VEGF is up-regulated in the ovine amnion when intramembranous absorption is augmented. In this study, we show that PBEF induced VEGF secretion by primary human amniotic epithelial cells (AEC) derived from the placental amnion, as well as from the reflected amnion that lines the remainder of the gestational sac. Further, PBEF treatment led to the increased expression of VEGFR2 in placental AEC, but not reflected AEC. To test the hypothesis that PBEF and VEGF increase placental amnion permeability, we monitored the transfer of 2′,7′-dichlorofluorescein (DCF) from the fetal to the maternal side of human amnion explants. A treatment regimen including both PBEF and VEGF increased the rate of DCF transfer across the placental amnion, but not the reflected amnion. In summary, our results suggest that by augmenting VEGFR2 expression in the placental amnion, PBEF primes the tissue for a VEGF-mediated increase in permeability. This mechanism may have important implications in amniotic fluid volume control throughout gestation.

The endocrine function of human placenta: an overview

“…In fact, it was reported visfatin increases in-vitro secretion of HPGH by primary human syncytiotrophoblasts (Zeck et al, 2008). Also, visfatin inhibits in-vitro contractility of human myometrium tissues (Mumtaz et al, 2015) and contributes to VEGF-mediated increase of human placental amnion's permeability by inducing VEGFR2 upregulation, indicating a role in the control of amniotic fluid volume throughout gestation (Astern et al, 2013). Moreover, visfatin also stimulates the release of prolabour mediators.…”

Transport-associated pathway responses in ovine fetal membranes to changes in amniotic fluid dynamics

“…), and pre‐ β cell colony‐enhancing factor (PBEF) which up‐regulates VEGF gene expression and increases VEGF receptor activities in amnion cells (Astern et al. ). In addition, we tested two potential inhibitors of VEGF activities: soluble fms‐like tyrosine kinase‐1 (sFlt‐1, sVEGF‐R1) (Kendall and Thomas ) which binds VEGF thus reduces VEGF bioavailability, and VEGF 164 b, a VEGF 164 isoform formed by alternate splicing of the VEGF gene, that antagonizes the VEGF receptor‐mediated downstream signaling pathways (Nowak et al.…”

Growth factors and their receptors derived from human amniotic cells in vitro

“…VEGF increases the permeability of the human amnion [2]. During pregnancy, amniotic fluid is constantly exchanged and deregulation of amniotic fluid volume may result in polyhydramnios or oligohydramnios, which are associated with preterm birth and perinatal morbidity or mortality [2].…”