Maternal immune stimulation reduces both placental morphologic damage and down-regulated placental growth-factor and cell cycle gene expression caused by urethane: are these events related to reduced teratogenesis?
Maternal immune stimulation reduces both placental morphologic damage and down-regulated placental growth-factor and cell cycle gene expression caused by urethane: are these events related to reduced teratogenesis?
复制标题
母体免疫刺激可减少尿烷引起的胎盘形态损伤以及胎盘生长因子和细胞周期基因表达的下调：这些事件是否与减少致畸有关？
DOI：
10.1016/s1567-5769(03)00093-6
复制
发表时间：
2003
影响因子：
5.6
通讯作者：
Holladay,SD
中科院分区：
文献类型：
--
作者：
Sharova,LV;Sharov,AA;Sura,P;Gogal,RM;Smith,BJ;Holladay,SD
激活小鼠的母体免疫系统可以减少由化学致畸剂氨基甲酸乙酯引起的腭裂。这种现象的直接和间接机制已经被提出，包括母体巨噬细胞穿过胎盘寻找和消除前畸形细胞，或者母体免疫蛋白(细胞因子)穿过胎盘减轻或部分减轻毒物在发育中的胎儿的影响。第三种机制可以解释胚胎发育结果的改善，可能涉及免疫刺激对胎盘的有益影响。在目前的实验中，乌拉坦治疗改变了胎盘的形态并损害了胎盘的功能，后者表现为细胞周期基因以及编码细胞因子和生长因子的基因的活性下调。使用弗氏完全佐剂或干扰素-γ的母体免疫刺激减少了氨甲酸酯对胎盘的形态损害，并减少了几个被乌拉坦下调的基因的正常表达。乌拉坦治疗还使胎盘细胞因子基因表达转向T细胞辅助者1(Th1)谱，而免疫刺激倾向于恢复Th2谱，这可能对怀孕和胎儿发育更有利。这些数据表明，母体免疫刺激对畸胎原暴露小鼠胎儿发育的有益影响可能部分是由于改善了胎盘的结构和功能。
Activation of the maternal immune system in mice decreased cleft palate caused by the chemical teratogen, urethane. Direct and indirect mechanisms for this phenomenon have been suggested, including maternal macrophages that cross the placenta to find and eliminate pre-teratogenic cells, or maternal immune proteins (cytokines) that cross placenta to alleviate or partially alleviate toxicant-mediated effects in the developing fetus. A third mechanism to explain improved fetal developmental outcome in teratogen-challenged pregnant mice might involve beneficial effects of immune stimulation on the placenta. In the present experiments, urethane treatment altered placental morphology and impaired placental function, the latter indicated by down-regulated activity of cell cycle genes and of genes encoding cytokines and growth factors. Maternal immune stimulation with either Freund's complete adjuvant (FCA) or interferon-gamma (IFNγ) reduced morphologic damage to the placenta caused by urethane and normalized expression of several genes that were down-regulated by urethane. Urethane treatment also shifted placental cytokine gene expression toward a T cell helper 1 (Th1) profile, while immunostimulation tended to restore a Th2 profile that may be more beneficial to pregnancy and fetal development. These data suggest that the beneficial effects of maternal immune stimulation on fetal development in teratogen-exposed mice may, in part, result from improved placental structure and function.