title: Cardiac defects, nuchal edema and abnormal lymphatic development are not associated with morphological changes in the ductus venosus.
abstract: In human fetuses with cardiac defects and increased nuchal translucency, abnormal ductus venosus flow velocity waveforms are observed. It is unknown whether abnormal ductus venosus flow velocity waveforms in fetuses with increased nuchal translucency are a reflection of altered cardiac function or are caused by local morphological alterations in the ductus venosus.
  
  
  
  The aim of this study was to investigate if the observed increased nuchal translucency, cardiac defects and abnormal lymphatic development in the examined mouse models are associated with local changes in ductus venosus morphology.
  
  
  
  Mouse embryos with anomalous lymphatic development and nuchal edema (Ccbe1(-/-) embryos), mouse embryos with cardiac defects and nuchal edema (Fkbp12(-/-), Tbx1(-/-), Chd7(fl/fl);Mesp1Cre, Jarid2(-/-NE+) embryos) and mouse embryos with cardiac defects without nuchal edema (Tbx2(-/-), Fgf10(-/-), Jarid2(-/-NE-) embryos) were examined. Embryos were analyzed from embryonic day (E) 11.5 to 15.5 using markers for endothelium, smooth muscle actin, nerve tissue and elastic fibers.
  
  
  
  All mutant and wild-type mouse embryos showed similar, positive endothelial and smooth muscle cell expression in the ductus venosus at E11.5-15.5. Nerve marker and elastic fiber expression were not identified in the ductus venosus in all investigated mutant and wild-type embryos. Local morphology and expression of the used markers were similar in the ductus venosus in all examined mutant and wild-type embryos.
  
  
  
  Cardiac defects, nuchal edema and abnormal lymphatic development are not associated with morphological changes in the ductus venosus. Ductus venosus flow velocity waveforms most probably reflect intracardiac pressure.
authors.affiliation: Department of Obstetrics and Gynecology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands. Electronic address: n.burger@vumc.nl.
authors.forename: Nicole B
authors.initials: NB
authors.lastname: Burger
authors.affiliation: Department of Obstetrics, Leiden University Medical Center, Albinusdreef 2 2333 ZA Leiden, the Netherlands. Electronic address: m.c.haak@lumc.nl.
authors.forename: Monique C
authors.initials: MC
authors.lastname: Haak
authors.affiliation: Department of Anatomy, Embryology & Physiology, Academic Medical Center, Meibergdreef 9 1105 AZ Amsterdam, the Netherlands. Electronic address: e.kok0602@gmail.com.
authors.forename: Evelien
authors.initials: E
authors.lastname: Kok
authors.affiliation: Department of Obstetrics and Gynecology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands. Electronic address: cj.degroot@vumc.nl.
authors.forename: Christianne J M
authors.initials: CJ
authors.lastname: de Groot
authors.affiliation: Riley Heart Research Center, Herman B Wells Center for Pediatric Research, Division of Pediatric Cardiology, Indiana University School of Medicine, 705 Riley Hospital Dr. Indianapolis, Indiana, USA. Electronic address: wshou@iu.edu.
authors.forename: Weinian
authors.initials: W
authors.lastname: Shou
authors.affiliation: Department of Molecular Medicine, University College London, Institute of Child Health, Gower Street, London, WC1E 6BT, United Kingdom. Electronic address: p.scambler@ucl.ac.uk.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Scambler
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin-Madison, 1111 Highland Ave. Madison, Wisconsin, USA. Electronic address: youngsooklee@wisc.edu.
authors.forename: Youngsook
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin-Madison, 1111 Highland Ave. Madison, Wisconsin, USA. Electronic address: echo36@wisc.edu.
authors.forename: Eunjin
authors.initials: E
authors.lastname: Cho
authors.affiliation: Department of Anatomy, Embryology & Physiology, Academic Medical Center, Meibergdreef 9 1105 AZ Amsterdam, the Netherlands. Electronic address: v.m.christoffels@amc.uva.nl.
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Christoffels
authors.affiliation: Department of Obstetrics and Gynecology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands. Electronic address: m.n.bekker-3@umcutrecht.nl.
authors.forename: Mireille N
authors.initials: MN
authors.lastname: Bekker
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001783:Blood Flow Velocity; D002135:Calcium-Binding Proteins / Q000235:genetics; D004487:Edema / Q000473:pathology*; D005260:Female; D051526:Fibroblast Growth Factor 10 / Q000235:genetics; D006330:Heart Defects, Congenital / Q000235:genetics / Q000473:pathology*; D008208:Lymphatic System / Q000002:abnormalities* / Q000473:pathology; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D053589:Nuchal Cord / Q000235:genetics / Q000473:pathology*; D048208:Nuchal Translucency Measurement; D063151:Polycomb Repressive Complex 2 / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics; D022061:Tacrolimus Binding Protein 1A / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D014471:Umbilical Veins / Q000473:pathology*
chemical_list: D000199:Actins; D002135:Calcium-Binding Proteins; C572375:Ccbe1 protein, mouse; C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; C093650:Jarid2 protein, mouse; C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins; C491573:Tbx1 protein, mouse; D025521:Tumor Suppressor Proteins; D063151:Polycomb Repressive Complex 2; D022061:Tacrolimus Binding Protein 1A
keywords: Cardiac defect; Ductus venosus; Endothelium; Increased nuchal translucency; Morphology; Nuchal edema