Systematic analysis of the development of the ductus venosus in wild type mouse and human embryos

Doppler flow velocities of the ductus venosus are increasingly used to assess fetal increased nuchal translucency, growth-restriction and monochorionic twins, and might contribute to screening for cardiac defects. It is disputed whether a sphincter at the ductus venosus inlet actively regulates blood flow. This study aims to define the morphogenesis of the developing mouse and human ductus venosus and to address the existence of a sphincter. The presence of endothelium, smooth muscle, elastic fibers and nerves in the ductus venosus of E10.5-15.5 mouse embryos and in three corresponding human embryos (CS16, CS19 and CS23) was examined using immunohistochemistry. Three-dimensional reconstructions of the ductus venosus of E11.5-15.5 mouse and CS14-23 human embryos were generated and examined. The ductus venosus lumen was narrowed from ventral-caudal to dorsal-cranial in E13.5-15.5 mouse and CS16-23 human embryos. Mouse embryos showed positive endothelial Pecam1 expression from E11.5-15.5 and smooth muscle actin staining in the ventral-caudal part of the ductus venosus from E12.5-15.5. At all developmental stages, elastic fiber and nerve marker expression was not detected in the ductus venosus (Fig. 2). In human embryos endothelial Pecam1 and smooth muscle actin expression was found in the ductus venosus from CS16 and CS19 onwards. Elastic fiber and nerve marker expression was not detected in all stages (Fig. 4). Morphogenesis and staining results of the ductus venosus were similar in both species. The ductus venosus lacks a sphincter at its inlet as no accumulation of smooth muscle cells, elastic fibers or nerve innervation was found in mouse embryos from E11.5-15.5 and in human embryos from CS14-23