title: The Transcription Factor NFIL3 Is Essential for Normal Placental and Embryonic Development but Not for Uterine Natural Killer (UNK) Cell Differentiation in Mice.
abstract: Mice ablated for the gene encoding the transcription factor Nfil3 lack peripheral natural killer (NK) cells but retain tissue-resident NK cells, particularly in mucosal sites, including virgin uterus. We undertook a time course histological study of implantation sites from syngeneically (Nfil3(-/-)) and allogeneically (BALB/c) mated Nfil3(-/-) females. We also examined implantation sites from Rag2(-/-)Il2rg(-/-) females preconditioned by adoptive transfer of Nfil3(-/-) marrow or uterine cell suspensions to identify the Nfil3(-/-) pregnancy aberrations that could be attributed to nonlymphoid cells. Uterine NKs (UNKs) reactive and nonreactive with the lectin Dolichos biflorus agglutinin (DBA) differentiate, localize, and mature within Nfil3(-/-) implantation sites, although at reduced abundance. The DBA nonreactive UNK cells were enriched following Nfil3(-/-) marrow transplantation. Uterine lumen closure, early embryonic development, and differentiation of antimesometrial decidua were delayed in Nfil3(-/-) implantation sites. Major disturbances to the decidual-trophoblast interface that did not lead to fetal death were attributed to NFIL3 deficiency in trophoblast. At midgestation, vessels of the placental labyrinth were enlarged, suggestive of reduced branching morphogenesis. A major term complication in most Nfil3(-/-) × Nfil3(-/-) pregnancies but not Nfil3(-/-) × Nfil3(+/-) pregnancies was dystocia. These studies highlight the differentiation potential and functions of Nfil3(-/-) UNK cell progenitors and illustrate that much of the implantation site histopathology associated with this strain is due to Nfil3 deletion in nonlymphoid cell lineages.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Mackenzie L
authors.initials: ML
authors.lastname: Redhead
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Nathália A
authors.initials: NA
authors.lastname: Portilho
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Allison M
authors.initials: AM
authors.lastname: Felker
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Shuhiba
authors.initials: S
authors.lastname: Mohammad
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Danielle L
authors.initials: DL
authors.lastname: Mara
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada croya@queensu.ca.
authors.forename: B Anne
authors.initials: BA
authors.lastname: Croy
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics*; D010064:Embryo Implantation / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D007694:Killer Cells, Natural / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010920:Placenta / Q000502:physiology*; D010929:Placentation / Q000235:genetics*; D011247:Pregnancy; D014599:Uterus / Q000276:immunology*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C497441:Nfil3 protein, mouse
keywords: decidua; fetal growth retardation; hematopoietic cell transplantation; spiral arterial modification; trophoblast