Induction of apoptosis in murine fetal thymocytes following perinatal exposure to diethylstilbestrol
Induction of apoptosis in murine fetal thymocytes following perinatal exposure to diethylstilbestrol
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DOI：
10.1080/10915810500488353
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发表时间：
2006-01-01
影响因子：
2.2
通讯作者：
Nagarkatti, PS
中科院分区：
文献类型：
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作者：
Brown, N;Nagarkatti, M;Nagarkatti, PS
已知围产期暴露于己烯雌酚（DES）可导致小鼠胸腺萎缩，但确切机制尚不清楚。在目前的研究中，作者调查了围产期暴露于DES是否会引发胸腺细胞凋亡。为此，将C57 BL/6妊娠小鼠腹膜内（i. p.）在妊娠第-15天和第-16天用5 μ g/kg DES。在gd-17、gd-19和出生后（PD）-1天从小鼠中收获的胸腺分析显示，仅在gd-17时胸腺细胞结构显著减少。此外，DES治疗显著改变了T细胞亚群的比例和绝对数量，特别是在gd-17。与对照组相比，DES处理的胸腺细胞凋亡增加，仅在GD-17上观察到。此外，DES处理的gd-17胸腺细胞具有增加的Asp-Glu-Val-Asp（DEVDase）活性。对GD-17胸腺细胞中96个凋亡基因的微阵列分析显示，暴露于DES增加了主要属于肿瘤坏死因子（TNF）和TNF受体（TNFR）家族的几个凋亡基因的表达。综上所述，这些结果表明，DES诱导的胸腺萎缩围产期暴露后，可能会导致，至少部分，从死亡受体途径介导的凋亡增加，涉及TNF家族成员。
Perinatal exposure to diethylstilbestrol (DES) is known to cause thymic atrophy in mice, although the precise mechanism remains unclear. In the current study the authors investigated whether perinatal exposure to DES would trigger apoptosis in thymocytes. To this end, C57BL/6 pregnant mice were injected intraperitoneally (i.p.) on gestational day (gd)-15 and -16 with 5 mu g/kg DES. Analysis of thymi harvested from mice on gd-17, gd-19 and postnatal day (PD)-1, showed a significant reduction in thymic cellularity on gd-17 only. Additionally, DES treatment significantly altered the proportion and absolute number of T-cell subsets, particularly on gd-17. Apoptosis was increased in DES-treated thymocytes when compared to the controls and was seen only on gd-17. Moreover, DES-treated gd-17 thymocytes had increased Asp-Glu-Val-Asp (DEVDase) activity. Microarray analysis of 96 apoptotic genes in gd-17 thymocytes revealed that exposure to DES increased the expression of several apoptotic genes primarily belonging to tumor necrosis factor (TNF) and TNF receptor (TNFR) family. Taken together, these results suggest that DES-induced thymic atrophy following perinatal exposure may result, at least in part, from increased apoptosis mediated by death receptor pathway involving TNF family members.