Angiogenin mediates paternal inflammation-induced metabolic disorders in offspring through sperm tsRNAs

Zhang, Yanwen; Ren, Li; Sun, Xiaoxiao; Zhang, Zhilong; Liu, Jie; Xin, Yining; Yu, Jianmin; Jia, Yimin; Sheng, Jinghao; Hu, Guo‐fu; Zhao, Ruqian; He, Bin

doi:10.1038/s41467-021-26909-1

Cited by 61 publications

(56 citation statements)

References 60 publications

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“…Treatment with ANG 1-7 lowered body weight, increased thermogenesis, and improved glucose homeostasis without changing food intake. Paternal inflammation-induced metabolic abnormalities in children are linked to ANG-mediated synthesis of 5'-tsRNAs in sperm, and offspring of inflamed fathers have metabolic diseases such as glucose intolerance and obesity ( 12 , 13 ).…”

Section: Discussionmentioning

confidence: 99%

Construction and Analysis of a Joint Diagnosis Model of Random Forest and Artificial Neural Network for Obesity

Xie

Zhang

et al. 2022

Front. Med.

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Obesity is a significant global health concern since it is connected to a higher risk of several chronic diseases. As a consequence, obesity may be described as a condition that reduces human life expectancy and significantly impacts life quality. Because traditional obesity diagnosis procedures have several flaws, it is vital to design new diagnostic models to enhance current methods. More obesity-related markers have been discovered in recent years as a result of improvements and enhancements in gene sequencing technology. Using current gene expression profiles from the Gene Expression Omnibus (GEO) collection, we identified differentially expressed genes (DEGs) associated with obesity and found 12 important genes (CRLS1, ANG, ALPK3, ADSSL1, ABCC1, HLF, AZGP1, TSC22D3, F2R, FXN, PEMT, and SPTAN1) using a random forest classifier. ALPK3, HLF, FXN, and SPTAN1 are the only genes that have never been linked to obesity. We also used an artificial neural network to build a novel obesity diagnosis model and tested its diagnostic effectiveness using public datasets.

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Section: Discussionmentioning

confidence: 99%

Construction and Analysis of a Joint Diagnosis Model of Random Forest and Artificial Neural Network for Obesity

Xie

Zhang

et al. 2022

Front. Med.

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“…Sperm sample collection and RNA extraction were performed as previously described [ 29 ]. The sperm were treated on ice with somatic cell lysis buffer for 40 min to eliminate somatic cell contamination.…”

Section: Methodsmentioning

confidence: 99%

“…Small RNA libraries were performed as previously described [ 29 ]. All RNA library preparation and quality examination were performed by BGI.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, sperm-borne small noncoding RNAs (sncRNAs) are being shown to transfer paternal epigenetic traits transgenerationally other than DNA [ 5 , 6 , 12 – 14 , 25 – 31 ]. We and others have reported that 30-40 nucleotide (nt) RNA fractions in sperm, such as transfer RNA-derived small RNAs (tsRNAs) and ribosomal RNA-derived small RNAs (rsRNAs), as well as their modifications, could be rapidly altered by environmental inputs such as unhealthy diets and toxicants, which then contribute to the intergenerational inheritance of metabolic disorders [ 5 , 6 , 25 , 29 , 32 , 33 ]. Also, sperm sncRNAs play a crucial role in the transgenerational modification of offspring addictive-like and anxiety-like behaviors [ 25 , 31 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

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Small Noncoding RNAs Contribute to Sperm Oxidative Stress-Induced Programming of Behavioral and Metabolic Phenotypes in Offspring

Ren

Xin

Sun

et al. 2022

Oxidative Medicine and Cellular Longevity

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There is growing evidence that paternal environmental information alters small noncoding RNAs (sncRNAs) in sperm and in turn can induce alterations of metabolic and behavioral phenotypes of the next generation. However, the potential mediators of the effects remain to be elucidated. A great diversity of environmental insults and stresses can convergently induce the elevation of reactive oxygen species (ROS) in sperm; nonetheless, it remains unclear whether ROS mediates the biogenesis of sncRNAs in sperm and participates in the reprogramming of offspring phenotypes. Here, we show that ROS could induce the alteration of sncRNA profiles in sperm, especially for transfer RNA-derived small RNAs (tsRNAs) and ribosomal RNA-derived small RNAs (rsRNAs). Zygotic injection of 29-34 nt RNA fractions (predominantly tsRNAs and rsRNAs) from oxidative stress (OS) sperm could induce depressive-like and anxiety-like behaviors in male offspring. Moreover, zygotic injection with synthetic RNAs partially resembled OS sperm-induced depressive-like and anxiety-like behaviors in offspring. Male offspring maintained on a chow diet was found to develop impaired glucose tolerance and hyperactive hepatic gluconeogenesis, accompanied by the upregulation of hepatic gluconeogenic and lipolytic genes. Together, our results have shown that ROS-induced alteration of sncRNA profiles in sperm contributes to the alterations of behavioral and metabolic phenotypes of the offspring.

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“…In a lipopolysaccharide (LPS)-induced epididymitis of rat model, a total of 1378 differentially expressed genes was identified compared with the controls through RNA sequencing, including 531 upregulated and 847 downregulated genes ( 13 ). Furthermore, a recent study stressed the critical function of tsRNA in transgenerational transmission induced by epididymal inflammation ( 14 ), the epigenetic contribution of inflammation in CE, particularly of small RNA and mRNA modifications, remains largely unexplored. Therefore, our study aims to analyze the small RNA landscape and transcriptional characteristics in human CE, as well as the potential correlation between them.…”

Section: Introductionmentioning

confidence: 99%

Integrative Analysis of Small RNA and mRNA Expression Profiles Identifies Signatures Associated With Chronic Epididymitis

et al. 2022

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Chronic epididymitis (CE) refers to a long-lasting inflammatory condition of the epididymis, which is considered the most common site of intrascrotal inflammation and an important aetiological factor of male infertility. Recent studies demonstrate that small RNAs secreted from epididymal epithelium modulate embryo development and offspring phenotypes via sperm transmission, and the resulting modifications may lead to transgenerational inheritance. However, to date, the genome-wide analysis of small RNA together with the transcriptomic expression profiles of human epididymis and CE is still lacking. In this study, we facilitated next-generation sequencing and bioinformatics to comprehensively analyze the small RNA and mRNA in an integrative way and identified signatures associated with CE. Both of the small RNA and mRNA expression data demonstrated relatively larger molecular differences among the segmental region of the epididymides, including caput, corpus, and cauda, than that of the inflammatory conditions. By comparing the inflamed caputs to the controls, a total of 1727 genes (1220 upregulated and 507 downregulated; 42 most significant genes, adjusted P <0.05) and 34 miRNAs (23 upregulated and 11 downregulated) were identified as differentially expressed. In silico functional enrichment analysis showed their roles in regulating different biological activities, including leukocyte chemotaxis, extracellular milieu reconstruction, ion channel and transporter-related processes, and nervous system development. Integrative analysis of miRNA and mRNA identified a regulatory network consisting of 22 miRNAs and 31 genes (miRNA-mRNA) which are strong candidates for CE. In addition, analysis about other species of small RNA, including (miRNA), piwi-interacting RNA (piRNA), tRNA-derived small RNA (tsRNA), Y RNA, and rsRNA identified the distinct expression pattern of tsRNA in CE. In summary, our study performed small RNA and miRNA profiling and integrative analysis in human CE. The findings will help to understand the role of miRNA-mRNA in the pathogenesis of CE and provide molecular candidates for the development of potential biomarkers for human CE.

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Angiogenin mediates paternal inflammation-induced metabolic disorders in offspring through sperm tsRNAs

Cited by 61 publications

References 60 publications

Construction and Analysis of a Joint Diagnosis Model of Random Forest and Artificial Neural Network for Obesity

Construction and Analysis of a Joint Diagnosis Model of Random Forest and Artificial Neural Network for Obesity

Small Noncoding RNAs Contribute to Sperm Oxidative Stress-Induced Programming of Behavioral and Metabolic Phenotypes in Offspring

Integrative Analysis of Small RNA and mRNA Expression Profiles Identifies Signatures Associated With Chronic Epididymitis

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