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产前地塞米松对雌性后代大鼠垂体和促性腺细胞的影响。

Effects of Prenatal Dexamethasone on the Rat Pituitary Gland and Gonadotropic Cells in Female Offspring.

作者信息

Ristić Nataša, Severs Walter, Nestorović Nataša, Jarić Ivana, Manojlović-Stojanoski Milica, Trifunović Svetlana, Pendovski Lazo, Milosević Verica

出版信息

Cells Tissues Organs. 2016;201(2):148-58. doi: 10.1159/000443987. Epub 2016 Mar 8.

Abstract

Glucocorticoids have a strong influence on growth and maturation of fetal organ systems, but overexposure to exogenous glucocorticoids may retard fetal growth and alter developmental processes in sensitive tissues. The aim of this study was to specifically determine whether prenatal exposure to dexamethasone (Dx) altered normal development and function of pituitary gonadotropic cells in neonatal, infant and peripubertal female offspring. On day 16 of pregnancy, rat dams received 1.0 mg Dx/kg body weight (BW) s.c., followed by 0.5 mg Dx/kg BW on days 17 and 18 of gestation. Control gravid females received the same volume of saline. Female offspring were sacrificed on days 5, 16 and 38 after delivery. The volume of the pituitary gland estimated using Cavalieri's principle was significantly reduced (p < 0.05). Using a fractionator-physical disector method, we found reduced total numbers of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) cells (p < 0.05), accompanied by a decrease (p < 0.05) in serum concentrations of FSH and LH, while the relative intensity of FSH and LH immunofluorescence remained unchanged in neonatal, infant and peripubertal female offspring prenatally exposed to Dx. The data document that overexposure to Dx during fetal development evokes developmental programming of the female reproductive system at the pituitary cellular level, which may be associated with impaired reproductive function.

摘要

糖皮质激素对胎儿器官系统的生长和成熟有强烈影响,但过度暴露于外源性糖皮质激素可能会阻碍胎儿生长并改变敏感组织中的发育过程。本研究的目的是具体确定产前暴露于地塞米松(Dx)是否会改变新生、婴儿和青春期前雌性后代垂体促性腺细胞的正常发育和功能。在妊娠第16天,大鼠母鼠皮下注射1.0 mg Dx/kg体重(BW),随后在妊娠第17天和18天注射0.5 mg Dx/kg BW。对照妊娠雌性大鼠注射相同体积的生理盐水。雌性后代在分娩后第5天、16天和38天处死。使用卡瓦列里原理估计的垂体体积显著减小(p<0.05)。使用分馏器-物理分割法,我们发现促卵泡激素(FSH)和促黄体生成素(LH)细胞的总数减少(p<0.05),同时血清FSH和LH浓度降低(p<0.05),而产前暴露于Dx的新生、婴儿和青春期前雌性后代中FSH和LH免疫荧光的相对强度保持不变。数据表明,胎儿发育期间过度暴露于Dx会在垂体细胞水平引发雌性生殖系统的发育编程,这可能与生殖功能受损有关。

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