水甘油通道蛋白AQP9促成了子宫内砷暴露对胎盘基因表达的性别特异性影响。
The aquaglyceroporin AQP9 contributes to the sex-specific effects of in utero arsenic exposure on placental gene expression.
作者信息
Winterbottom Emily F, Koestler Devin C, Fei Dennis Liang, Wika Eric, Capobianco Anthony J, Marsit Carmen J, Karagas Margaret R, Robbins David J
机构信息
Molecular Oncology Program, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
出版信息
Environ Health. 2017 Jun 14;16(1):59. doi: 10.1186/s12940-017-0267-8.
BACKGROUND
Sex-specific factors play a major role in human health and disease, including responses to environmental stresses such as toxicant exposure. Increasing evidence suggests that such sex differences also exist during fetal development. In a previous report using the resources of the New Hampshire Birth Cohort Study (NHBCS), we found that low-to-moderate in utero exposure to arsenic, a highly toxic and widespread pollutant, was associated with altered expression of several key developmental genes in the fetal portion of the placenta. These associations were sex-dependent, suggesting that in utero arsenic exposure differentially impacts male and female fetuses. In the present study, we investigated the molecular basis for these sex-specific responses to arsenic.
METHODS
Using NanoString technology, we further analyzed the fetal placenta samples from the NHBCS for the expression of genes encoding arsenic transporters and metabolic enzymes. Multivariable linear regression analysis was used to examine their relationship with arsenic exposure and with key developmental genes, after stratification by fetal sex.
RESULTS
We found that maternal arsenic exposure was strongly associated with expression of the AQP9 gene, encoding an aquaglyceroporin transporter, in female but not male fetal placenta. Moreover, AQP9 expression associated with that of a subset of female-specific arsenic-responsive genes.
CONCLUSIONS
Our results suggest that AQP9 is upregulated in response to arsenic exposure in female, but not male, fetal placenta. Based on these results and prior studies, increased AQP9 expression may lead to increased arsenic transport in the female fetal placenta, which in turn may alter the expression patterns of key developmental genes that we have previously shown to be associated with arsenic exposure. Thus, this study suggests that AQP9 may play a role in the sex-specific effects of in utero arsenic exposure.
背景
性别特异性因素在人类健康和疾病中起着重要作用，包括对环境压力（如接触有毒物质）的反应。越来越多的证据表明，这种性别差异在胎儿发育过程中也存在。在之前一项利用新罕布什尔州出生队列研究（NHBCS）资源的报告中，我们发现，子宫内低至中度接触砷（一种剧毒且广泛存在的污染物）与胎盘胎儿部分中几个关键发育基因的表达改变有关。这些关联具有性别依赖性，表明子宫内砷暴露对雄性和雌性胎儿的影响不同。在本研究中，我们调查了对砷的这些性别特异性反应的分子基础。
方法
我们使用NanoString技术，进一步分析了NHBCS中胎儿胎盘样本中编码砷转运蛋白和代谢酶的基因表达情况。在按胎儿性别分层后，使用多变量线性回归分析来检查它们与砷暴露以及关键发育基因之间的关系。
结果
我们发现，母亲砷暴露与雌性而非雄性胎儿胎盘中编码水甘油通道蛋白转运体的AQP9基因的表达密切相关。此外，AQP9的表达与一组雌性特异性砷反应基因的表达相关。
结论
我们的结果表明，在雌性而非雄性胎儿胎盘中，AQP9会因砷暴露而上调。基于这些结果和先前的研究，AQP9表达增加可能导致雌性胎儿胎盘中砷转运增加，这反过来可能会改变我们之前发现的与砷暴露相关的关键发育基因的表达模式。因此，本研究表明AQP9可能在子宫内砷暴露的性别特异性影响中起作用。
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