Bakker J M, Schmidt E D, Kroes H, Kavelaars A, Heijnen C J, Tilders F J, van Rees E P
Department of Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit, Amsterdam, Netherlands.
J Neuroimmunol. 1995 Dec 31;63(2):183-91. doi: 10.1016/0165-5728(95)00152-2.
The effects of glucocorticoid (GC) treatment on the mature immune and neuroendocrine system are known to be reversible. However, prenatal GC exposure may have irreversible consequences on the development of the newborn. In this study, possible long-lasting effects of short-term prenatal GC treatment were examined on the developing thymus, spleen and hypothalamo-pituitary adrenal axis (HPA axis). Female rats were given dexamethasone (DEX, 400 micrograms, i.p.) on day 17 and 19 of pregnancy and offspring was studied at several time intervals (1-20 days) after birth, for examination of thymus, spleen, hypothalamus and blood plasma. Examination of thymus and spleen revealed that prenatal exposure to DEX resulted in decreased T cell numbers in thymus and spleen on day 1 after birth. Thymus regeneration after DEX exposure both during pregnancy and in adult life was completed after 24 days. However, the kinetics of regeneration of the thymi after prenatal DEX exposure were different from that seen after DEX in adult life. Whereas DEX treatment during pregnancy resulted in an increased ratio of CD4+/CD8- thymocytes over CD4-/CD8+ thymocytes compared to control groups on day 7 and day 20 after birth (time X treatment interaction; P < 0.05), DEX treatment in adult life did not change this ratio. T cell numbers in the spleen were significantly decreased at all neonatal ages studied. Regarding the hypothalamus, prenatal exposure to DEX altered the pattern of neonatal changes in peptide expression in corticotropin-releasing hormone neurons, with a selective reduction in CRH storage in the median eminence (7 and 9 days after birth) and an increase in AVP storage (9 and 20 days after birth). The ratio of AVP over CRH was significantly increased at all developmental ages studied. No effects were seen on basal ACTH and corticosterone levels in plasma. In conclusion, the kinetics of thymus regeneration after DEX exposure during pregnancy were different from that seen after DEX exposure in adult life. Prenatal DEX exposure also seemed to delay the migration of T cells into the spleen. Furthermore, prenatal DEX treatment exerted major effects on hypothalamic CRH neurons that maintained for at least 20 days after birth, which points towards an enhanced stress responsiveness of the HPA axis in later life.
已知糖皮质激素（GC）治疗对成熟的免疫系统和神经内分泌系统的影响是可逆的。然而，产前暴露于GC可能会对新生儿的发育产生不可逆的后果。在本研究中，研究了短期产前GC治疗对发育中的胸腺、脾脏和下丘脑-垂体-肾上腺轴（HPA轴）可能产生的长期影响。在妊娠第17天和第19天给雌性大鼠腹腔注射地塞米松（DEX，400微克），并在出生后的几个时间间隔（1 - 20天）对后代进行研究，以检查胸腺、脾脏、下丘脑和血浆。胸腺和脾脏检查显示，产前暴露于DEX导致出生后第1天胸腺和脾脏中的T细胞数量减少。孕期和成年期暴露于DEX后胸腺的再生在24天后完成。然而，产前暴露于DEX后胸腺再生的动力学与成年期暴露于DEX后不同。与对照组相比，孕期DEX治疗导致出生后第7天和第20天CD4 + / CD8 - 胸腺细胞与CD4 - / CD8 + 胸腺细胞的比例增加（时间×治疗交互作用；P < 0.05），而成年期DEX治疗并未改变这一比例。在所研究的所有新生儿年龄段，脾脏中的T细胞数量均显著减少。关于下丘脑，产前暴露于DEX改变了促肾上腺皮质激素释放激素神经元中肽表达的新生儿变化模式，在正中隆起中CRH储存选择性减少（出生后7天和9天），AVP储存增加（出生后9天和20天）。在所研究的所有发育年龄段，AVP与CRH的比例均显著增加。对血浆中基础促肾上腺皮质激素（ACTH）和皮质酮水平未见影响。总之,孕期暴露于DEX后胸腺再生的动力学与成年期暴露于DEX后不同。产前暴露于DEX似乎也延迟了T细胞向脾脏的迁移。此外，产前DEX治疗对下丘脑CRH神经元产生了主要影响，这种影响在出生后至少持续20天，这表明后期生活中HPA轴的应激反应性增强。
