Abstract

Objectives: Fetuses with increased nuchal translucency (NT) morphologically show nuchal edema (NE), accompanied by distended jugular lymphatic sacs (JLS). Also, previous research demonstrated a loss of lymphatic identity of the endothelium of these JLS accompanied by abnormal smooth muscle cell (SMC) formation surrounding the JLS. FOXC2 suppresses the expression of plateletderived growth factor-beta (PDGF-B) in lymphatic endothelial cells which is essential for SMC-attraction and proliferation. Therefore, we investigated FOXC2 and PDGF-B expression in the endothelium of the enlarged JLS in trisomy 21 fetuses. Methods: Four trisomy 21 fetuses (gestational ages 13–14 weeks) were compared with four control fetuses (gestational ages 12–14 weeks). The expression of FOXC2 and PDGF-B in the endothelium of the JLS was investigated using immunohistochemistry. Furthermore, endothelial differentiation was investigated using lymphatic markers and blood vessel markers. Smooth muscle actin was used as a smooth muscle cell marker. Results: The trisomy 21 fetuses with NE showed enlarged JLS as compared with the controls. Also, erythrocytes were demonstrated in the JLS of trisomy 21 fetuses. A decreased expression of lymphatic markers was found in the endothelium of the JLS of the NE fetuses compared with controls. An addition, the enlarged JLS showed blood vessel characteristics in contrast to the control fetuses. SMC were found surrounding the JLS in case of trisomy 21 in contrast to the controls. Furthermore, a decreased FOXC2 expression and increased PDGF-B expression in the endothelium of the JLS was found in the trisomy 21 fetuses compared with the control fetuses. Conclusions: Altered FOXC2 and PDGF-B expression is related to abnormal SMC formation surrounding the enlarged JLS in trisomy 21 fetuses with nuchal edema.

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