Microarray profiling of LncRNA expression in the testis of pubertal mice following morning and evening exposure to 1800 MHz radiofrequency fields
Microarray profiling of LncRNA expression in the testis of pubertal mice following morning and evening exposure to 1800 MHz radiofrequency fields
复制标题
早晚暴露于 1800 MHz 射频场后青春期小鼠睾丸中 LncRNA 表达的微阵列分析
DOI：
10.1080/07420528.2021.1962902
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发表时间：
2021-08-06
影响因子：
2.8
通讯作者：
Pei，Hailong
中科院分区：
文献类型：
--
作者：
Qin，Fenju;Cao，Honglong;Pei，Hailong
本文通过4周龄小鼠每天早晚暴露于射频(1800 MHz，SAR，0.50W/kg)，研究了射频对青春期睾丸发育的时序毒性及其相关的分子途径。然后测定睾丸组织的病理改变和功能指标。我们还使用了一个长的非编码RNA(LncRNA)微阵列和GO/KEGG通路分析来确定lncRNA的表达谱并预测它们的潜在功能。研究了lncRNAs的顺式和反式调控，并利用Cytoscape软件构建了相互作用网络。RF暴露导致青春期小鼠睾丸的一系列病理变化，睾丸重量和每日精子产量减少，睾酮分泌减少。此外，RF还可诱导睾丸组织中lncRNAs的表达异常。我们鉴定了615个和183个差异表达的lncRNA，它们分别与早晨和晚上暴露于RF有关。从早晚RF组差异表达的15个LncRNAs中筛选出6个LncRNAs用于定量逆转录聚合酶链式反应(qRT-PCR)。这些差异表达的lncRNAs与许多不同的途径密切相关，包括Fanconi综合征、代谢过程、细胞周期、DNA损伤和DNA复制。反式调节分析进一步表明，差异表达的lncRNAs参与了多种转录因子调控的途径，如TCFAP4、NFkB、HINFP、TFDP2、FOXN1和PAX5。这些转录因子都被证明参与了睾丸发育、细胞周期进程和精子发生的调节。这些结果表明，1800 MHz射频对睾丸的毒性和对lncRNAs表达的改变程度在早间暴露和晚间暴露之间存在差异。这些数据表明，差异表达的lncRNAs在射频暴露对发育中的青春期睾丸的损伤中起着关键作用。总而言之，我们的发现有助于更好地理解射频暴露对睾丸发育的毒性影响的潜在机制。
ABSTRACT In this paper, the chronotoxicity of radiofrequency fields (RF) in the pubertal testis development and the involved molecular pathways were investigated by exposing four-week-old mice to RF (1800 MHz, SAR, 0.50 W/kg) in the morning and evening of each day for three weeks. Then, pathological changes and functional indices within the testis were determined. We also used a long non-coding RNA (lncRNA) microarray and GO/KEGG pathway analyses to determine lncRNA expression profiles and predict their potential functions. The cis and trans regulation of lncRNAs were investigated, and an interaction network was constructed using Cytoscape software. RF exposure led to a range of pathological changes in the testes of adolescent mice, as testicular weights and daily sperm productions decreased, and the testosterone secretion reduced. Furthermore, RF induced dysregulation in the expression of testicular lncRNAs. We identified 615 and 183 differentially expressed lncRNAs that were associated with morning and evening exposure to RF, respectively. From 15 differential expression lncRNAs both in morning RF group and evening RF group, we selected 6 lncRNAs to be validated by quantitative reverse transcription PCR (qRT-PCR). The differentially expressed lncRNAs induced by morning RF exposure were highly correlated with many different pathways, including Fanconi syndrome, metabolic processes, cell cycle, DNA damage, and DNA replication. Trans-regulation analyses further showed that differentially expressed lncRNAs were involved in multiple transcription factor-regulated pathways, such as TCFAP4, NFkB, HINFP, TFDP2, FoxN1, and PAX5. These transcription factors have all been shown to be involved in the modulation of testis development, cell cycle progression, and spermatogenesis. These findings suggest that the extent to which 1800 MHz RF induced toxicity in the testes and changed the expression of lncRNAs showed differences between morning exposure and evening exposure. These data indicate that differentially expressed lncRNAs play crucial roles in the RF exposure damage to the developing pubertal testis. Collectively, our findings provide a better understanding of the mechanisms underlying the toxic effects of RF exposure on testicular development.