Maternal bisphenol a exposure impacts the fetal heart transcriptome.
Maternal bisphenol a exposure impacts the fetal heart transcriptome.
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DOI：
10.1371/journal.pone.0089096
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Murdoch GK
中科院分区：
文献类型：
--
作者：
Chapalamadugu KC;Vandevoort CA;Settles ML;Robison BD;Murdoch GK
胎儿发育期间的状况会影响成年后的健康和疾病，特别是在器官发生的关键时期。胎儿接触内分泌干扰物双酚A(BPA)会影响啮齿动物和猴子多器官系统的发育。然而，双酚A暴露对心脏发育的影响尚未得到评估。有证据表明，母体双酚A是通过胎盘传递给发育中的胎儿的，因此在灵长类动物发育过程中检查妊娠暴露的生理后果变得势在必行。在这里，我们评估了每日口服双酚A对怀孕恒河猴(猕猴)胎心转录组的影响。妊娠猴在妊娠早期(妊娠后50~100±2天)或妊娠晚期(100±2天)每日口服双酚A(400微克/千克体重)。在治疗结束时，收集胎儿心脏组织，利用全基因组微阵列评估房间特异性转录组的表达。对筛选出的基因进行实时定量聚合酶链式反应，定量测定心肌组织糖原含量。我们的结果表明，双酚A暴露改变了被认为在心脏病理生理学中起作用的基因的转录。重要的是，肌球蛋白重链，心脏亚型α(MYH6)在左心室下调，‘A去整合素和金属蛋白酶12’，长亚型(Adam12-L)在两个心室和右心房上调。双酚A诱导的这些基因的改变支持了胎儿发育期间暴露于双酚A可能影响心血管健康的假说。我们的结果加剧了人们对双酚A在人类代谢和心血管疾病发生中的作用的担忧。
Conditions during fetal development influence health and disease in adulthood, especially during critical windows of organogenesis. Fetal exposure to the endocrine disrupting chemical, bisphenol A (BPA) affects the development of multiple organ systems in rodents and monkeys. However, effects of BPA exposure on cardiac development have not been assessed. With evidence that maternal BPA is transplacentally delivered to the developing fetus, it becomes imperative to examine the physiological consequences of gestational exposure during primate development. Herein, we evaluate the effects of daily, oral BPA exposure of pregnant rhesus monkeys (Macaca mulatta) on the fetal heart transcriptome. Pregnant monkeys were given daily oral doses (400 µg/kg body weight) of BPA during early (50–100±2 days post conception, dpc) or late (100±2 dpc – term), gestation. At the end of treatment, fetal heart tissues were collected and chamber specific transcriptome expression was assessed using genome-wide microarray. Quantitative real-time PCR was conducted on select genes and ventricular tissue glycogen content was quantified. Our results show that BPA exposure alters transcription of genes that are recognized for their role in cardiac pathophysiologies. Importantly, myosin heavy chain, cardiac isoform alpha (Myh6) was down-regulated in the left ventricle, and ‘A Disintegrin and Metalloprotease 12’, long isoform (Adam12-l) was up-regulated in both ventricles, and the right atrium of the heart in BPA exposed fetuses. BPA induced alteration of these genes supports the hypothesis that exposure to BPA during fetal development may impact cardiovascular fitness. Our results intensify concerns about the role of BPA in the genesis of human metabolic and cardiovascular diseases.
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DOI：
10.1083/jcb.200612046
发表时间：
2007-07-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Atfi A;Dumont E;Colland F;Bonnier D;L'helgoualc'h A;Prunier C;Ferrand N;Clément B;Wewer UM;Théret N
通讯作者：
Théret N
影响因子：
10.4
作者：
Alonso-Magdalena P;Vieira E;Soriano S;Menes L;Burks D;Quesada I;Nadal A
通讯作者：
Nadal A
DOI：
10.1073/pnas.1207854109
发表时间：
2012-10-23
影响因子：
11.1
作者：
Hunt, Patricia A.;Lawson, Crystal;VandeVoort, Catherine A.
通讯作者：
VandeVoort, Catherine A.
影响因子：
4.7
作者：
Buterin, Tonko;Koch, Caroline;Naegeli, Hanspeter
通讯作者：
Naegeli, Hanspeter
影响因子：
6.6
作者：
Danzi, Sara;Klein, Steven;Klein, Irwin
通讯作者：
Klein, Irwin