title: Hectd1 is required for development of the junctional zone of the placenta.
abstract: The placenta plays a critical role in the growth and survival of the fetus. Here we demonstrate that the Homologous to the E6-AP Carboxyl Terminus (HECT) domain E3 ubiquitin ligase, Hectd1, is essential for development of the mouse placenta. Hectd1 is widely expressed during placentation with enrichment in trophoblast giant cells (TGCs) and other trophoblast-derived cell subtypes in the junctional and labyrinth zones of the placenta. Disruption of Hectd1 results in mid-gestation lethality and intrauterine growth restriction (IUGR). Variable defects in the gross structure of the mutant placenta are found including alterations in diameter, thickness and lamination. The number and nuclear size of TGCs is reduced. Examination of subtype specific markers reveals altered TGC development with decreased expression of Placental lactogen-1 and -2 (Pl1 and Pl2) and increased expression of Proliferin (Plf). Reduced numbers of spongiotrophoblasts and glycogen trophoblasts were also found at the junctional zone of the Hectd1 mutant placenta. Finally, there was an increase in immature uterine natural killer (uNK) cells in the maternal decidua of the Hectd1 mutant placenta. Proliferation and apoptosis are differentially altered in the layers of the placenta with an increase in both apoptosis and proliferation in the maternal decidua, a decrease in proliferation and increase in apoptosis in the labyrinth layer and both unchanged in the junctional zone. Together these data demonstrate that Hectd1 is required for development of multiple cell types within the junctional zone of the placenta.
authors.affiliation: Center for Neuroscience Research, Children׳s Research Institute, and Children׳s National Medical Center, Washington, DC 20010, USA.
authors.forename: Anjali A
authors.initials: AA
authors.lastname: Sarkar
authors.affiliation: Center for Neuroscience Research, Children׳s Research Institute, and Children׳s National Medical Center, Washington, DC 20010, USA.
authors.forename: Samer J
authors.initials: SJ
authors.lastname: Nuwayhid
authors.affiliation: Department of Pharmacology and Physiology, The George Washington Institute for Neuroscience, George Washington University, Washington, DC 20052, USA; The George Washington Institute for Neuroscience, George Washington University, Washington, DC 20052, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Maynard
authors.affiliation: Center for Neuroscience Research, Children׳s Research Institute, and Children׳s National Medical Center, Washington, DC 20010, USA.
authors.forename: Frederick
authors.initials: F
authors.lastname: Ghandchi
authors.affiliation: University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Jonathon T
authors.initials: JT
authors.lastname: Hill
authors.affiliation: Department of Pharmacology and Physiology, The George Washington Institute for Neuroscience, George Washington University, Washington, DC 20052, USA; The George Washington Institute for Neuroscience, George Washington University, Washington, DC 20052, USA.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Lamantia
authors.affiliation: Center for Neuroscience Research, Children׳s Research Institute, and Children׳s National Medical Center, Washington, DC 20010, USA; Department of Pharmacology and Physiology, The George Washington Institute for Neuroscience, George Washington University, Washington, DC 20052, USA; The George Washington Institute for Neuroscience, George Washington University, Washington, DC 20052, USA. Electronic address: izohn@cnmcresearch.org.
authors.forename: Irene E
authors.initials: IE
authors.lastname: Zohn
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D005260:Female; D015726:Giant Cells / Q000166:cytology / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism; D051379:Mice; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D010928:Placental Lactogen / Q000378:metabolism; D010929:Placentation; D011247:Pregnancy; D011388:Prolactin; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C000634106:Prl2c2 protein, mouse; D011388:Prolactin; D010928:Placental Lactogen; C521132:Hectd1 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: HECT E3 ligase; Placenta; Trophoblast