Original Paper

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Abnormal Shh and FOXC2 expression correlates with aberrant lymphatic development in human fetuses with increased nuchal translucency

  1. Yolanda M. de Mooij1,2,
  2. Nynke M. S. van den Akker1,3,
  3. Mireille N. Bekker2,
  4. Margot M. Bartelings1,
  5. Lambertus J. Wisse1,
  6. John M. G. van Vugt2,
  7. Adriana C. Gittenberger-de Groot1,*

Article first published online: 22 JUN 2009

DOI: 10.1002/pd.2316

Issue

Prenatal Diagnosis

Prenatal Diagnosis

Volume 29, Issue 9, pages 840–846, September 2009

Additional Information

How to Cite

de Mooij, Y. M., van den Akker, N. M. S., Bekker, M. N., Bartelings, M. M., Wisse, L. J., van Vugt, J. M. G. and Gittenberger-de Groot, A. C. (2009), Abnormal Shh and FOXC2 expression correlates with aberrant lymphatic development in human fetuses with increased nuchal translucency. Prenatal Diagnosis, 29: 840–846. doi: 10.1002/pd.2316

Author Information

  1. 1

    Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands

  2. 2

    Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam, The Netherlands

  3. 3

    Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands

*Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, P.O. Box 9600, 2300 RC Leiden, The Netherlands.

Publication History

  1. Issue published online: 28 AUG 2009
  2. Article first published online: 22 JUN 2009
  3. Manuscript Accepted: 16 MAY 2009
  4. Manuscript Revised: 29 APR 2009
  5. Manuscript Received: 4 MAR 2009

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Keywords:

  • nuchal translucency;
  • lymphatic development;
  • Shh;
  • FOXC2;
  • jugular lymphatic sac

Abstract

Objective

Previous research in fetuses with increased nuchal translucency (NT) showed abnormal lymphatic endothelial differentiation characteristics, including increased vascular endothelial growth factor (VEGF)-A expression, and aberrant smooth muscle cells (SMCs) surrounding enlarged jugular lymphatic sacs (JLS). We hypothesized that abnormal Sonic hedgehog (Shh) expression would result in altered VEGF-A signaling in the lymphatic endothelial cells of the JLS and that aberrant acquisition of SMCs could be caused by downregulation of forkhead transcription factor FOXC2 and upregulation of platelet-derived growth factor (PDGF)-B in the lymphatic endothelial cells of the JLS.

Methods

Five trisomy 21 fetuses and four controls were investigated using immunohistochemistry for Shh, VEGF-A, FOXC2 and PDGF-B expression in the lymphatic endothelial cells of the JLS.

Results

An increased Shh, VEGF-A and PDGF-B expression, and decreased FOXC2 expression were shown in the lymphatic endothelial cells of the JLS of the trisomic fetuses.

Conclusions

Increased Shh and VEGF-A expression is correlated with an aberrant lymphatic endothelial differentiation in trisomy 21 fetuses. The SMCs surrounding the JLS can possibly be explained by an increase of PDGF-B-induced SMC recruitment and/or differentiation. This underscores earlier findings that indicate the loss of lymphatic identity in trisomy 21 fetuses and a shift towards a blood vessel wall phenotype. Copyright © 2009 John Wiley & Sons, Ltd.

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