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Published on: February 2, 2016
Abnormal Shh and FOXC2 expression correlates with aberrant lymphatic development in human fetuses with increased
Yolanda M de Mooij1, Nynke M S van den Akker, Mireille N Bekker
1Department of Anatomy and Embryology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
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.
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