Allergic asthma is a chronic pulmonary disorder fundamentally linked to immune dysfunction. Since the immune system begins developing in utero, prenatal exposures can affect immune programming and increase risk for diseases such as allergic asthma. Chronic psychosocial stress during pregnancy is one such risk factor, having been associated with increased risk for atopic diseases including allergic asthma in children. To begin to define the underlying causes of the association between maternal stress and allergic airway inflammation in offspring, we developed a mouse model of chronic heightened stress hormone during pregnancy. Continuous oral administration of corticosterone (CORT) to pregnant mice throughout the second half of pregnancy resulted in an ~2-fold increase in circulating hormone in dams with no concomitant increase in fetal circulation, similar to the human condition. To determine how prolonged heightened stress hormone affected allergic immunity in offspring, we induced allergic asthma with house dust mite (HDM) and examined the airway immune response to allergen. Female mice responded to HDM more frequently and had a more robust immune cell response compared to their male counterparts, irrespective of maternal treatment. Male offspring from CORT-treated dams had a greater number of inflammatory cells in the lung in response to HDM compared to males from control dams, while maternal treatment did not affect immune cell numbers in females. Alternatively, maternal CORT caused enhanced goblet cell hyperplasia in female offspring following HDM, an effect that was not observed in male offspring. In summary, prenatal exposure to mild, prolonged heightened stress hormone had sexually dimorphic effects on allergic inflammation in airways of adult offspring.

中文翻译：

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小鼠怀孕期间慢性升高的母体皮质酮会增加后代的过敏性气道炎症。

过敏性哮喘是一种根本上与免疫功能障碍相关的慢性肺部疾病。由于免疫系统开始在子宫内发育，产前暴露会影响免疫程序并增加诸如过敏性哮喘等疾病的风险。怀孕期间的慢性社会心理压力就是这样的危险因素之一，与儿童过敏性哮喘（包括过敏性哮喘）的风险增加相关。为了开始确定母体压力与后代过敏性气道炎症之间关联的潜在原因，我们开发了小鼠妊娠期慢性应激激素水平升高的小鼠模型。在整个怀孕的下半年，对怀孕的小鼠连续口服皮质酮（CORT）可使大坝中的循环激素增加约2倍，而胎儿的循环却没有随之增加，类似于人类的状况。为了确定长期升高的应激激素如何影响后代的过敏性免疫，我们用屋尘螨（HDM）诱发了过敏性哮喘，并检查了气道对过敏原的免疫反应。与雄性雌性小鼠相比，雌性小鼠对HDM的反应更为频繁，并且免疫细胞反应更为强烈，无论其母体治疗如何。与对照大坝的雄性相比，CORT处理过的大坝的雄性后代对HDM的肺部炎症细胞数量更多，而母体治疗并不影响雌性的免疫细胞数量。或者，母亲CORT导致HDM后雌性后代的杯状细胞增生增强，而在雄性后代中未观察到这种作用。总之，产前暴露于轻度，