Increased nuchal translucency origins from abnormal lymphatic development and is independent of the presence of a cardiac defect

Abstract

Objective: To assess whether cardiac failure, because of cardiac defects, and abnormal jugular lymphatic development are involved in nuchal edema (NE) - the morphological equivalent of increased nuchal translucency - in various euploid mutant mouse models.

Method: Mouse embryos with lymphatic abnormalities and NE (Ccbe1(-/-)), with cardiac defects and NE (Fkbp12(-/-), Tbx1(-/-), Chd7(fl/fl);Mesp1Cre, Jarid2(-/-NE+)) and with cardiac malformations without NE (Tbx2(-/-), Pitx2(-/-), Fgf10(-/-), Jarid2(-/-NE-)) were examined. Embryos were analyzed from embryonic day 11.5 to 15.5. Markers for lymphatic vessels, endothelium, smooth muscle cells and nerves were used to study the nuchal region. Hematoxylin-Azophloxine staining was performed to examine cardiac morphology.

Results: Mouse embryos with lymphatic abnormalities and NE (Ccbe1(-/-)) showed no formation of the jugular lymphatic sac but normal cardiac morphology. In mouse embryos with cardiac defects and NE (Fkbp12(-/-), Tbx1(-/-), Chd7(fl/fl);Mesp1Cre, Jarid2(-/-NE+)) enlarged jugular lymphatic sacs or large nuchal cavities within the NE were found. In mouse embryos with a cardiac malformation without NE (Tbx2(-/-), Pitx2(-/-), Fgf10(-/-), Jarid2(-/-NE-)) normal jugular lymphatic sacs were observed.

Conclusion: NE consistently coincides with abnormal jugular lymphatic development in euploid mouse embryos, independent of cardiac anatomy. NE is unlikely to be caused by temporary cardiac failure solely because of a cardiac defect.