The association between smoking and ectopic pregnancy: why nicotine is BAD for your fallopian tube.
The association between smoking and ectopic pregnancy: why nicotine is BAD for your fallopian tube.
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DOI：
10.1371/journal.pone.0089400
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Duncan WC
中科院分区：
文献类型：
--
作者：
Horne AW;Brown JK;Nio-Kobayashi J;Abidin HB;Adin ZE;Boswell L;Burgess S;Lee KF;Duncan WC
流行病学研究表明，吸烟是输卵管异位妊娠的主要危险因素，但其原因尚不清楚。在这里，我们开始确定吸烟对输卵管基因表达的影响。将输卵管上皮细胞系（OE-E6/E7）和未怀孕妇女（n = 6）的人输卵管外体暴露于生理相关浓度的尼古丁主要代谢物可替宁中，并使用Illumina human HT-12阵列分析基因表达的变化。然后利用免疫组织化学和TaqMan RT-PCR，在非怀孕吸烟者（n = 10）和非吸烟者（n = 11）的输卵管活检中定位和量化通过该过程鉴定的可替宁敏感基因。阵列分析显示，可替宁诱导的外植体和细胞系基因表达变化主要是促凋亡基因BAD的显著下调（P<0.05）。因此，我们在回顾性收集的人类样本中评估了吸烟对细胞更新的影响。与阵列数据一致，吸烟与输卵管活检中BAD转录物水平降低（P<0.01）和BCL2转录物水平升高（P<0.05）相关。BAD和BCL2特异性免疫标记定位于输卵管上皮。虽然在细胞凋亡和细胞周期相关蛋白水平上没有观察到其他显著差异，但吸烟与输卵管上皮形态的显著变化相关（P<0.05）。这些结果表明，吸烟可能改变输卵管上皮细胞的更新，并与结构和功能变化有关，这些变化可能导致异位妊娠的发生。
Epidemiological studies have shown that cigarette smoking is a major risk factor for tubal ectopic pregnancy but the reason for this remains unclear. Here, we set out to determine the effect of smoking on Fallopian tube gene expression. An oviductal epithelial cell line (OE-E6/E7) and explants of human Fallopian tubes from non-pregnant women (n = 6) were exposed to physiologically relevant concentrations of cotinine, the principle metabolite of nicotine, and changes in gene expression analyzed using the Illumina Human HT-12 array. Cotinine sensitive genes identified through this process were then localized and quantified in Fallopian tube biopsies from non-pregnant smokers (n = 10) and non-smokers (n = 11) using immunohistochemistry and TaqMan RT-PCR. The principle cotinine induced change in gene expression detected by the array analysis in both explants and the cell line was significant down regulation (P<0.05) of the pro-apoptotic gene BAD. We therefore assessed the effect of smoking on cell turnover in retrospectively collected human samples. Consistent with the array data, smoking was associated with decreased levels of BAD transcript (P<0.01) and increased levels of BCL2 transcript (P<0.05) in Fallopian tube biopsies. BAD and BCL2 specific immunolabelling was localized to Fallopian tube epithelium. Although no other significant differences in levels of apoptosis or cell cycle associated proteins were observed, smoking was associated with significant changes in the morphology of the Fallopian tube epithelium (P<0.05). These results suggest that smoking may alter tubal epithelial cell turnover and is associated with structural, as well as functional, changes that may contribute to the development of ectopic pregnancy.
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