Redhead Mackenzie L, Portilho Nathália A, Felker Allison M, Mohammad Shuhiba, Mara Danielle L, Croy B Anne
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada
Biol Reprod. 2016 May;94(5):101. doi: 10.1095/biolreprod.116.138495. Epub 2016 Mar 16.
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.
编码转录因子Nfil3的基因被敲除的小鼠缺乏外周自然杀伤（NK）细胞，但保留了组织驻留NK细胞，特别是在包括未孕子宫在内的黏膜部位。我们对同基因（Nfil3(-/-)）和异基因（BALB/c）交配的Nfil3(-/-)雌性小鼠的着床部位进行了时间进程组织学研究。我们还检查了通过移植Nfil3(-/-)骨髓或子宫细胞悬液进行预处理的Rag2(-/-)Il2rg(-/-)雌性小鼠的着床部位，以确定可归因于非淋巴细胞的Nfil3(-/-)妊娠异常。与凝集素双花扁豆凝集素（DBA）反应性和非反应性的子宫NK细胞（UNK）在Nfil3(-/-)着床部位分化、定位并成熟，尽管数量减少。Nfil3(-/-)骨髓移植后，DBA非反应性UNK细胞增多。Nfil3(-/-)着床部位的子宫腔闭合、早期胚胎发育以及反系膜蜕膜的分化均延迟。蜕膜-滋养层界面的主要紊乱但未导致胎儿死亡归因于滋养层中NFIL3的缺乏。在妊娠中期，胎盘迷路的血管扩张，提示分支形态发生减少。大多数Nfil3(-/-)×Nfil3(-/-)妊娠而非Nfil3(-/-)×Nfil3(+/-)妊娠的主要足月并发症是难产。这些研究突出了Nfil3(-/-)UNK细胞祖细胞的分化潜能和功能，并表明与该品系相关的许多着床部位组织病理学是由于非淋巴细胞谱系中Nfil3的缺失。
