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Genome-wide microRNA expression analysis in human placenta reveals sex-specific patterns: an ENVIRONAGE birth cohort study
Epigenetics ( IF 2.9 ) Pub Date : 2020-09-06
Maria Tsamou, Karen Vrijens, Congrong Wang, Ellen Winckelmans, Kristof Y. Neven, Narjes Madhloum, Theo M. de Kok, Tim S. Nawrot

There is an increasing interest in microRNAs (miRNAs) as they are of utmost importance in gene regulation at the posttranscriptional level. Sex-related susceptibility for non-communicable diseases later in life could originate in early life. Until now, no data on sex-specific miRNA expression are available for the placenta. Therefore, we investigated the difference by sex of newborn’s miRNA expression in human placental tissue. Within the ENVIRONAGE birth cohort, miRNA and mRNA expression profiling was performed in 60 placentae (50% boys) using Agilent (8 × 60 K) microarrays. The distribution of chromosome locations was studied and pathway analysis of the identified sex-specific miRNAs in the placenta was carried out. Of the total 2558 miRNAs on the array, 597 miRNAs were expressed in over 70% of the samples and were included for further analyses. A total of 142 miRNAs were significantly (FDR<0.05) associated with the newborn’s sex. In newborn girls, 76 miRNAs had higher expression (hsa-miR-361-5p as most significant) and 66 miRNAs had lower expression (hsa-miR-4646-5p as most significant) than in newborn boys. In the same study population, placental differentially expressed genes by sex were also identified using a whole genome approach. The placental gene expression revealed 27 differentially expressed genes by comparing girls to boys. Ultimately, we studied the miRNA-RNA interactome and identified 14 miRNA–mRNA interactions as sex-specific. Sex differences in placental m(i)RNA expression may reveal sex-specific patterns already present during pregnancy, which may influence physiological conditions in early or later life. These molecular processes might play a role in sex-specific disease susceptibility in later life.



中文翻译:

人类胎盘全基因组microRNA表达分析揭示性别特异性模式:一项环境出生队列研究

由于microRNA(miRNA)在转录后水平的基因调控中极为重要,因此人们对此越来越感兴趣。生命后期与非传染性疾病有关的性别敏感性可能起源于生命早期。到目前为止,尚无有关性别特异性miRNA表达的数据可用于胎盘。因此,我们调查了在人胎盘组织中新生儿miRNA表达的性别差异。在ENVIR ON内使用安捷伦(8×60 K)微阵列在60个胎盘(50%男孩)中进行AGE出生队列,miRNA和mRNA表达谱分析。研究了染色体位置的分布,并对胎盘中已鉴定的性别特异性miRNA进行了通路分析。在阵列上总共2558个miRNA中,有597个miRNA在超过70%的样品中表达,并被包括在内以进行进一步分析。共有142个miRNA与新生儿性别显着相关(FDR <0.05)。在新生女孩中,与新生男孩相比,有76个miRNA的表达较高(hsa-miR-361-5p最显着),而有66个miRNA的表达较低(hsa-miR-4646-5p最显着)。在同一研究人群中,还使用全基因组方法鉴定了按性别区分的胎盘差异表达基因。通过比较女孩和男孩,胎盘基因表达揭示了27个差异表达的基因。最终,我们研究了miRNA-RNA相互作用基因组,并确定了14种miRNA-mRNA相互作用为性别特异性。胎盘m(i)RNA表达的性别差异可能揭示怀孕期间已经存在的性别特异性模式,这可能会影响早期或晚年的生理状况。这些分子过程可能在以后的性别特异性疾病易感性中起作用。

更新日期:2020-09-07
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