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16 March 2016 The Transcription Factor NFIL3 Is Essential for Normal Placental and Embryonic Development but Not for Uterine Natural Killer (UNK) Cell Differentiation in Mice
Mackenzie L. Redhead, Nathália A. Portilho, Allison M. Felker, Shuhiba Mohammad, Danielle L. Mara, B. Anne Croy
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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.

Mackenzie L. Redhead, Nathália A. Portilho, Allison M. Felker, Shuhiba Mohammad, Danielle L. Mara, and B. Anne Croy "The Transcription Factor NFIL3 Is Essential for Normal Placental and Embryonic Development but Not for Uterine Natural Killer (UNK) Cell Differentiation in Mice," Biology of Reproduction 94(5), (16 March 2016). https://doi.org/10.1095/biolreprod.116.138495
Received: 10 January 2016; Accepted: 1 March 2016; Published: 16 March 2016
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