Reduced expression of the epidermal growth factor signaling system in preeclampsia. Issue 3 (March 2015)

• Record Type: Journal Article
• Authors: Armant, D.R.; Fritz, R.; Kilburn, B.A.; Kim, Y.M.; Nien, J.K.; Maihle, N.J.; Romero, R.; Leach, R.E.
• Is Part Of: Placenta. Volume 36:Issue 3(2015:Mar.)
• Page Start: 270
• Page End: 278
• Publication Date: 2015-03
• Subjects: Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2014.12.006
• Languages: English
• ISSNs: 0143-4004

Abstract

<abstract xml:lang="en" abstract-type="author" id="abs0010"> <title id="sectitle0010">Abstract</title> <sec> <title id="sectitle0015">Introduction</title> <p id="abspara0010">The epidermal growth factor (EGF) signaling system regulates trophoblast differentiation, and its disruption could contribute to perinatal disease. We hypothesized that this pathway is altered in preeclampsia, a disorder associated with trophoblast apoptosis and failure to invade and remodel the uterine spiral arteries.</p> </sec> <sec> <title id="sectitle0020">Methods</title> <p id="abspara0015">Six EGF family peptides and a truncated EGF receptor splice variant (p110/EGFR) were examined using immunohistochemistry in the trophoblast of placentas (N = 76) from women with preeclampsia, and compared to placentas from women of similar gestational age (GA) with preterm labor (PTL) or small for gestational age (SGA) fetuses, as well as normal term placentas. EGF, transforming growth factor-α (TGFA), and heparin-binding EGF-like growth factor (HBEGF) were evaluated using ELISA in maternal plasma from another 20 pregnancies with or without preeclampsia. Cell death was evaluated in the HTR-8/SVneo human cytotrophoblast cell line using TUNEL to evaluate the protective effects of EGF peptides.</p> </sec> <sec> <title id="sectitle0025">Results</title> <p id="abspara0020">Trophoblast HBEGF, TGFA, and EGF were significantly reduced in preeclampsia compared to PTL and SGA, while p110/EGFR accumulated significantly on the surface of the chorionic villi (<italic>p</italic> < 0.05). Plasma EGF levels were significantly decreased in preeclamptic patients, compared to non-preeclamptic patients (<italic>p</italic> < 0.05). HBEGF, EGF, TGFA, epiregulin, and betacellulin each blocked cytotrophoblast cell death <italic>in vitro</italic> (<italic>p</italic> < 0.05).</p> </sec> <sec> <title id="sectitle0030">Discussion</title> <p id="abspara0025">Three members of the EGF family are dysregulated in placentas with preeclampsia, whereas p110/EGFR, a potential EGF receptor antagonist, is overexpressed. These findings are consistent with the concept that disruption of the EGF signaling system contributes to aberrant trophoblast development associated with preeclampsia.</p> </sec> </abstract>