PRENATAL ALCOHOL EXPOSURE--IMMUNE/ENDOCRINE INTERACTIONS

怀孕期间母亲饮酒的不良影响包括 关于胎儿酒精中毒儿童严重免疫缺陷的报道 与年龄匹配的对照组进行比较。胎鼠模型的建立 酒精暴露(FAE)已证明在过去的一年中酒精暴露 怀孕两周会产生长期的T细胞缺陷 功能，主要是在雄性后代身上。然而，到目前为止，还没有研究表明 评估了怀孕期间饮酒的机制 会损害后代的免疫功能。 饮酒改变母体荷尔蒙的产生 影响胎儿免疫功能的发育。观察到的是 阿司匹林对成年FAE雄性大鼠T细胞功能的影响 母亲肾上腺切除术表明母亲的肾上腺激素 参与FAE胎儿的免疫抑制“印记”。 因此，实验被设计成专注于描述荷尔蒙的特征 导致这种产前性二型性效应的成分 酒精暴露对T细胞功能的影响。 这项建议的目的是：1.描述酒精暴露对 慢性阻塞性肺疾病患者肾上腺/性腺激素分泌谱及血浆激素水平 结果：1.正常妊娠大鼠和去肾上腺妊娠大鼠均为正常妊娠大鼠； 确定母亲肾上腺切除和产前酒精的效果 暴露对男女胎儿胸腺功能发育的影响 胎儿和选定的T细胞的细胞和分子参数 在成年男性和女性肾上腺切除酒精的后代中的作用- 消耗大坝；3.确定糖皮质激素或任何其他 已知会影响免疫功能的类固醇激素被发现 在具体目标1中确定的酒精中毒的上升，是 负责免疫抑制的“印记”的男性和 以及这种类固醇是否会影响胎儿胸腺的发育 直接和性别--具体地说，或通过长期的性 糖皮质激素、雌激素或雌激素表达的二形性变化 后代中的雄激素受体；以及4.最终确定 弱雄激素脱氢表雄酮的产前给药 糖皮质激素受体拮抗剂，已知的抑制作用 特定的疾病过程，会消除免疫抑制作用 孕期酒精暴露对雄性后代的影响。

Adverse effects of maternal alcohol consumption during pregnancy include the severe immunodeficiencies reported in children with fetal alcohol syndrome compared to age matched controls. Animal models of fetal alcohol exposure (FAE) have proved that alcohol exposure during the last two weeks of gestation can produce long-lasting defects of T-cell function, primarily in male offspring. However, no studies to date have assessed the mechanism by which alcohol consumption during pregnancy compromises the offspring's immune function. Alcohol consumption alters production of maternal hormones that can affect the development of fetal immune function. The observation that suppressed T-cell function in adult FAE male rat was abolished by maternal adrenalectomy suggests that maternal adrenal hormones do participate in the immunosuppressive "imprinting" of the FAE fetus. Thus, experiments are designed to focus on characterizing the hormonal components responsible for this sexually dimorphic effect of prenatal alcohol exposure on T-cell function. This proposal seeks: 1. to delineate the effect of alcohol exposure on the secretory profile and plasma levels of adrenal/gonadal steroids in the intact and adrenalectomized pregnant rat throughout gestation; 2. to determine the effect of maternal adrenalectomy and prenatal alcohol exposure on fetal development of thymic functions in male and female fetuses, and on selected cellular and molecular parameters of T-cell function, in adult male and female offspring of adrenalectomized alcohol- consuming dams; 3. to determine whether glucocorticoids, or any other steroid hormones that are known to affect immune function and were found to be elevated in alcoholism as established in Specific Aims 1, are responsible for the immunosuppressive "imprinting" of the FAE male and female fetus, and whether this steroid affects fetal thymic development directly and gender-specifically, or through long-term, sexually dimorphic changes in the expression of glucocorticoid, estrogen or androgen receptors in the offspring; and 4. finally to determine whether prenatal administration of dehydroepiandrosterone, a weak androgen and glucocorticoid receptor antagonist with known inhibitory effects on specific disease processes, will eliminate the immunosuppressive effect of prenatal alcohol exposure on the male offspring.