Reduced levels of maternal progesterone during pregnancy increase the risk for allergic airway diseases in females only
Reduced levels of maternal progesterone during pregnancy increase the risk for allergic airway diseases in females only
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怀孕期间母体黄体酮水平降低只会增加女性患过敏性气道疾病的风险
DOI：
10.1007/s00109-014-1167-9
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Pincus M
中科院分区：
文献类型：
--
作者：
Hartwig IR;Bruenahl CA;Ramisch K;Keil T;Inman M;Arck PC;Pincus M
摘要观察和实验研究表明，产前挑战似乎与后代过敏性气道疾病风险增加有关。然而，对调节这种风险的生物标志物的了解很大程度上是难以捉摸的。我们的目的是测试孕妇记录的内源性和外源性因素之间的关联，包括社会心理、内分泌和生活方式参数，以及儿童以后患过敏性气道疾病的风险。我们进一步对过敏性气道反应小鼠模型中已确定的因素进行功能测试。在前瞻性设计的妊娠队列（n = 409 个家庭）中，招募了怀孕第 4 周至第 12 周的女性。为了调查怀孕期间暴露与 3 至 5 岁儿童过敏性气道疾病发病率之间的关联，应用了多重逻辑回归分析。此外，在产前应激的 BALB/c 交配 BALB/c 雌性小鼠的成年后代中，通过卵清蛋白 (OVA) 致敏实验诱导了哮喘。除了产前应激挑战外，一些怀孕女性还接受了黄体酮衍生物二氢地屈孕酮（DHD）的治疗。在人类中，我们观察到，人类妊娠早期母体孕酮水平较高与女儿患过敏性气道疾病（哮喘或过敏性鼻炎）的风险降低相关（调整后 OR 0.92；95% 置信区间 [CI] 0.84 至 1.00），但与儿子无关（aOR 1.02，95% CI 0.94-1.10）。在小鼠中，对遭受应激的母鼠进行产前 DHD 补充，仅在雌性后代中减轻了产前应激诱导的气道高反应性。怀孕期间母体黄体酮水平降低（可能由高压力感知引起）会增加女性患过敏性气道疾病的风险，但不会增加男性患过敏性气道疾病的风险。关键信息怀孕期间母体黄体酮水平较低只会增加女性后代患过敏性气道疾病的风险。产前补充黄体酮可改善产前应激小鼠后代的气道高反应性。
AbstractObservational as well as experimental studies support that prenatal challenges seemed to be associated with an increased risk for allergic airway diseases in the offspring. However, insights into biomarkers involved in mediating this risk are largely elusive. We here aimed to test the association between endogenous and exogenous factors documented in pregnant women, including psychosocial, endocrine, and life style parameters, and the risk for allergic airway diseases in the children later in life. We further pursued to functionally test identified factors in a mouse model of an allergic airway response. In a prospectively designed pregnancy cohort (n= 409 families), women were recruited between the 4th and 12th week of pregnancy. To investigate an association between exposures during pregnancy and the incidence of allergic airway disease in children between 3 and 5 years of age, multiple logistic regression analyses were applied. Further, in prenatally stressed adult offspring of BALB/c-mated BALB/c female mice, asthma was experimentally induced by ovalbumin (OVA) sensitization. In addition to the prenatal stress challenge, some pregnant females were treated with the progesterone derivative dihydrodydrogesterone (DHD). In humans, we observed that high levels of maternal progesterone in early human pregnancies were associated with a decreased risk for an allergic airway disease (asthma or allergic rhinitis) in daughters (adjusted OR 0.92; 95 % confidence interval [CI] 0.84 to 1.00) but not sons (aOR 1.02, 95 % CI 0.94-1.10). In mice, prenatal DHD supplementation of stress-challenged dams attenuated prenatal stress-induced airway hyperresponsiveness exclusively in female offspring. Reduced levels of maternal progesterone during pregnancy—which can result from high stress perception—increase the risk for allergic airway diseases in females but not in males.Key messagesLower maternal progesterone during pregnancy increases the risk for allergic airway disease only in female offspring.Prenatal progesterone supplementation ameliorates airway hyperreactivity in prenatally stressed murine offspring.
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