Guo Tai L, Meng Andrew H
Department of Veterinary Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7382, United States.
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298-0613, United States.
Toxicol Lett. 2016 Jun 24;253:17-26. doi: 10.1016/j.toxlet.2016.04.017. Epub 2016 Apr 22.
Despite many hypothesized benefits of dietary isoflavone genistein (GEN) deriving from soy-based products, questions surrounding GEN's developmental immunotoxic effects are increasing. To understand how in utero GEN exposure may modulate postnatal respiratory sensitization, we conducted a time course study using a common household allergen (house dust mites: HDM; 10μg/mouse) following intranasal instillation, a physiological route of allergen exposure. GEN was administered to dams by gavage from gestational day 14 to parturition at a physiologically relevant dose (20mg/kg bw). Female and male offspring were sensitized with HDM allergens beginning about one month prior to sacrifice followed by challenges with three weekly doses of HDM extracts, and they were euthanized at day 3 following the final HDM exposure at four different time points (postnatal day (PND) 80, 120, 160, and 200). In utero GEN combined with postnatal HDM exposures (GEN+HDM) increased total IgE production in both young female and male B6C3F1 offspring (e.g., PND 80 in females and PND 120 in males). Increased antigen-specific IgG1, IgG2a and IgG2b levels were also observed at various time points in both female and male offspring. In addition, increases in macrophage number in bronchoalveolar lavage fluid of both female and male GEN+HDM offspring at PND 80 and PND 120, respectively, were observed when compared to the vehicle group. For T cells, an increase over the vehicle in female GEN+HDM offspring was observed at PND 80. Due to similar patterns of increases, it seems likely that GEN+HDM-induced increases in total IgE and macrophages are related. Overall, in utero GEN plus later-life HDM exposures exert increases in total IgE and HDM-specific IgG production as well as macrophage recruitments to the lung in young adult mice.
尽管源自大豆制品的膳食异黄酮染料木黄酮（GEN）有许多假定的益处，但围绕GEN的发育免疫毒性作用的问题却日益增多。为了解子宫内GEN暴露如何调节产后呼吸道致敏作用，我们进行了一项时间进程研究，在经鼻滴注（一种过敏原暴露的生理途径）后，使用一种常见的家用过敏原（屋尘螨：HDM；10μg/小鼠）。从妊娠第14天至分娩，以生理相关剂量（20mg/kg体重）通过灌胃法将GEN给予母鼠。雌性和雄性后代在处死前约一个月开始用HDM过敏原致敏，随后每周三次给予HDM提取物进行激发，并在四个不同时间点（出生后第（PND）80、120、160和200天）最后一次HDM暴露后第3天实施安乐死。子宫内GEN联合产后HDM暴露（GEN+HDM）增加了年轻雌性和雄性B6C3F1后代的总IgE产生（例如，雌性在PND 80，雄性在PND 120）。在雌性和雄性后代的不同时间点也观察到抗原特异性IgG1、IgG2a和IgG2b水平升高。此外，与载体组相比，在PND 80和PND 120时，雌性和雄性GEN+HDM后代支气管肺泡灌洗液中的巨噬细胞数量分别增加。对于T细胞，在PND 80时观察到雌性GEN+HDM后代相对于载体组有所增加。由于增加模式相似，GEN+HDM诱导的总IgE和巨噬细胞增加似乎有关联。总体而言，子宫内GEN加上成年后HDM暴露会使年轻成年小鼠的总IgE和HDM特异性IgG产生增加，以及巨噬细胞向肺部募集增加。
