Reduced expression of the epidermal growth factor signaling system in preeclampsia

D. R. Armant, R. Fritz, B. A. Kilburn, Y. M. Kim, J. K. Nien, N. J. Maihle, R. Romero, R. E. Leach

Research output: Contribution to journalArticle

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Abstract

Introduction 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. Methods 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. Results 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 (p < 0.05). Plasma EGF levels were significantly decreased in preeclamptic patients, compared to non-preeclamptic patients (p < 0.05). HBEGF, EGF, TGFA, epiregulin, and betacellulin each blocked cytotrophoblast cell death in vitro (p < 0.05). Discussion 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.

Original languageEnglish (US)
Pages (from-to)270-278
Number of pages9
JournalPlacenta
Volume36
Issue number3
DOIs
StatePublished - Mar 1 2015

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Pre-Eclampsia
Epidermal Growth Factor
Trophoblasts
Placenta
Transforming Growth Factors
Gestational Age
Premature Obstetric Labor
Epidermal Growth Factor Receptor
Cell Death
Chorionic Villi
Uterine Artery
Peptides
In Situ Nick-End Labeling
Heparin
Intercellular Signaling Peptides and Proteins
Fetus
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Mothers
Apoptosis

Keywords

  • Epidermal growth factors
  • Placenta
  • Preeclampsia

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Developmental Biology

Cite this

Armant, D. R., Fritz, R., Kilburn, B. A., Kim, Y. M., Nien, J. K., Maihle, N. J., ... Leach, R. E. (2015). Reduced expression of the epidermal growth factor signaling system in preeclampsia. Placenta, 36(3), 270-278. https://doi.org/10.1016/j.placenta.2014.12.006

Reduced expression of the epidermal growth factor signaling system in preeclampsia. / Armant, D. R.; Fritz, R.; Kilburn, B. A.; Kim, Y. M.; Nien, J. K.; Maihle, N. J.; Romero, R.; Leach, R. E.

In: Placenta, Vol. 36, No. 3, 01.03.2015, p. 270-278.

Research output: Contribution to journalArticle

Armant, DR, Fritz, R, Kilburn, BA, Kim, YM, Nien, JK, Maihle, NJ, Romero, R & Leach, RE 2015, 'Reduced expression of the epidermal growth factor signaling system in preeclampsia', Placenta, vol. 36, no. 3, pp. 270-278. https://doi.org/10.1016/j.placenta.2014.12.006
Armant DR, Fritz R, Kilburn BA, Kim YM, Nien JK, Maihle NJ et al. Reduced expression of the epidermal growth factor signaling system in preeclampsia. Placenta. 2015 Mar 1;36(3):270-278. https://doi.org/10.1016/j.placenta.2014.12.006
Armant, D. R. ; Fritz, R. ; Kilburn, B. A. ; Kim, Y. M. ; Nien, J. K. ; Maihle, N. J. ; Romero, R. ; Leach, R. E. / Reduced expression of the epidermal growth factor signaling system in preeclampsia. In: Placenta. 2015 ; Vol. 36, No. 3. pp. 270-278.
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