Hussey Michael R, Burt Amber, Deyssenroth Maya A, Jackson Brian P, Hao Ke, Peng Shouneng, Chen Jia, Marsit Carmen J, Everson Todd M
Department of Environmental Health, Rollins School of Public Health at Emory University, Atlanta, GA, USA.
Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Environ Epigenet. 2020 May 10;6(1):dvaa003. doi: 10.1093/eep/dvaa003. eCollection 2020 Jan.
Heavy metal exposures, such as cadmium, can have negative effects on infant birth weight (BW)-among other developmental outcomes-with placental dysfunction potentially playing a role in these effects. In this study, we examined how differential placental expression of long non-coding RNAs (lncRNAs) may be associated with cadmium levels in placenta and whether differences in the expression of those lncRNAs were associated with fetal growth. In the Rhode Island Child Health Study, we used data from Illumina HiSeq whole transcriptome RNA sequencing ( = 199) to examine association between lncRNA expression and measures of infant BW as well as placental cadmium concentrations controlled for appropriate covariates. Of the 1191 lncRNAs sequenced, 46 demonstrated associations ( < 0.05) with BW in models controlling for infant sex, maternal age, BMI, maternal education, and smoking during pregnancy. Furthermore, four of these transcripts were associated with placental cadmium concentrations, with and demonstrating increases in expression associated with increasing cadmium exposure and elevated odds of small for gestational age birth, while and demonstrated reduced expression associated with cadmium, but elevated odds of large for gestational age birth with increasing expression. We identified relationships between lncRNA expression with both placental cadmium concentrations and BW. This study provides evidence that disrupted placental expression of lncRNAs may be a part of cadmium's mechanisms of reproductive toxicity.
接触镉等重金属可能会对婴儿出生体重（BW）以及其他发育结果产生负面影响，胎盘功能障碍可能在这些影响中发挥作用。在本研究中，我们研究了长链非编码RNA（lncRNA）在胎盘中的差异表达如何与胎盘中的镉水平相关，以及这些lncRNA的表达差异是否与胎儿生长相关。在罗德岛儿童健康研究中，我们使用了来自Illumina HiSeq全转录组RNA测序的数据（n = 199），以研究lncRNA表达与婴儿出生体重测量值以及控制了适当协变量的胎盘镉浓度之间的关联。在测序的1191个lncRNA中，有46个在控制婴儿性别、母亲年龄、体重指数、母亲教育程度和孕期吸烟的模型中显示出与出生体重的关联（P < 0.05）。此外，其中四个转录本与胎盘镉浓度相关，[具体基因1]和[具体基因2]显示随着镉暴露增加表达增加，且小于胎龄儿出生几率升高，而[具体基因3]和[具体基因4]显示与镉相关的表达降低，但随着表达增加大于胎龄儿出生几率升高。我们确定了lncRNA表达与胎盘镉浓度和出生体重之间的关系。这项研究提供了证据，表明lncRNA在胎盘中的表达紊乱可能是镉生殖毒性机制的一部分。
