In utero exposure to genistein decreased intranasal house dust mite-induced respiratory allergy in middle-aged male B6C3F1 offspring.

In utero exposure to genistein decreased intranasal house dust mite-induced respiratory allergy in middle-aged male B6C3F1 offspring.
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DOI:
10.1016/j.toxlet.2020.07.013
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发表时间:
2020-10-15
期刊:
影响因子:
3.5
通讯作者:
Meng AH
Meng AH
中科院分区:
医学3区
文献类型:
--
作者:
Guo TL;Lefever DE;Nagy T;Meng AH

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尽管大豆制品对饮食中的异黄酮染料木素(Gen)有许多假定的益处,但围绕Gen的发育影响的问题越来越多。为了了解宫内暴露是否调节了中年出生后呼吸道过敏,我们在B6C3F1后代(PND240-330)中进行了一项时间进程研究,使用一种常见的家庭变应原(屋尘螨:HDM;PND240和290为10μg/只,PND330为50μg/只,中年小鼠),鼻内滴注,这是过敏原暴露的一种生理途径。从妊娠第14天起至分娩,母鼠按生理剂量(20 mg/kg体重)灌胃给予GEN。雌性和雄性后代在处死前一个月开始用HDM变应原致敏,然后每周注射三次HDM提取物,并在最后一次接触HDM后的第三天对它们进行安乐死。宫内暴露于GEN可降低PND 330的雄性B6C3F1后代由HDM过敏原引起的呼吸道过敏反应,表现为呼吸道高反应性(如Penh值)、HDM特异性IgG1(Th2型抗体)和肺中嗜酸粒细胞过氧化物酶活性(嗜酸性粒细胞向肺部募集的指标)的降低。然而,宫内暴露于GEN对中年雌性后代中HDM变应原诱导的呼吸道过敏的影响很小。雄性和雌性后代的血清总IgE、HDM特异性IgE和肺组织病理学评分的变化没有生物学意义。总体而言,宫内接触HDM对中年男性B6C3F1后代的呼吸过敏起到了保护作用,但对女性没有影响。
Despite many hypothesized benefits of dietary isoflavone genistein (GEN) deriving from soy-based products, questions surrounding GEN’s developmental effects are increasing. To understand if in utero GEN exposure modulated postnatal respiratory allergies in the middle age, we conducted a time course study in the B6C3F1 offspring (PND 240–330) using a common household allergen (house dust mites: HDM; 10 μg/mouse for PND 240 and 290, and 50 μg/mouse for PND 330, a middle age in mice) 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 (20 mg/kg body weight). Female and male offspring were sensitized with HDM allergens beginning about one month prior to sacrifice followed by challenges with three weekly dosings of HDM extracts, and they were euthanized at day 3 following the final HDM exposure. In utero exposure to GEN decreased HDM allergen-induced respiratory allergy in male B6C3F1 offspring at PND 330 as reflected by decreases in airway hyperresponsiveness (e.g., Penh value), HDM-specific IgG1 (a Th2 type Ab) and the activity of eosinophil peroxidase in the lung (an indication of eosinophil recruitment to the lungs). However, in utero exposure to GEN had minimal effects on HDM allergen-induced respiratory allergy in the middle-aged female offspring. Changes in serum total IgE, HDM-specific IgE, and lung histopathology scores in both male and female offspring were not biologically significant. Overall, in utero GEN exposure exerted a protective effect on respiratory allergy in the middle-aged male, but not female, B6C3F1 offspring following later-life HDM exposures.
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