Smoking induces differential miRNA expression in human spermatozoa: A potential transgenerational epigenetic concern?

Marczylo, Emma L.; Amoako, Akwasi; Konje, Justin C.; Gant, Timothy W.; Marczylo, Timothy H.

doi:10.4161/epi.19794

Cited by 202 publications

(130 citation statements)

References 52 publications

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“…Another study revealed that the predominant pathways mediated by miRNAs differentially expressed in the sperm of smokers were involved in cell proliferation, differentiation and death, pathways important during spermatogenesis and early embryo development. Thus, indicating potential epigenetic role for miRNAs in the multigenerational toxicity of cigarette smoke [33]. Diet can also alter miRNA expression and have transgenerational consequences as demonstrated in a study conducted by Fullston et al (2013).…”

Section: Sperm Mirna and Transgenerational Inheritancementioning

confidence: 97%

Sperm-Specific MicroRNAs - Their Role and Function

Al-Gazi¹,

Carroll²

2016

GGS

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The sperm cell is highly specialised, with the sole purpose to fertilize an oocyte. Sperm assumes a simplistic structure, consisting of a head, which is mostly void of cytoplasm, a nucleus packed with DNA tightly wound around protamines; a midpiece housing the mitochondria necessary to fuel its locomotion, and a tail or principle piece that whips in motion to move the sperm towards the oocyte. However, despite the lack of cytoplasmic space, increasing studies in sperm biology have revealed that the sperm cell contains a myriad of molecular constituents that may play a role post-fertilization, influencing the oocyte and embryo development (figure 1). One such group of molecules are the small non-coding RNAs, which include the microRNAs (miRNAs). microRNAs miRNAs are small non-coding single-strand RNA molecules with sizes ranging from 17-26 nucleotides. The first miRNA to be discovered was lin-4 in the nematode, Caenorhabditis elegans. Lin-4 was detected with conserved complementary site on lin-14 and subsequently affected the larvae developmental timing by targeting mRNA and inhibiting its function [1]. Since then, miRNAs have emerged to play key roles in many biological functions through binding to 3'UTR (Untranslated Region) of specific mRNAs leading to either mRNA degradation or protein translation inhibition [2]. These miRNAs are involved in regulating cell functions including gene expression during development, differentiation, cell proliferation and apoptosis [3,4].In addition to having an influence in normal biological and developmental processes, miRNAs have been found to be involved in many pathogenic processes including Cardiovascular Diseases (CVD), cancer, inflammatory or autoimmune diseases, metabolic disorders and neurodegenerative disorders [5]. miRNA biogenesis miRNAs are encoded in the genome and transcribed by RNA polymerase II to form long primary miRNA transcripts (pri-miRNAs) that contain a cap structure at the 5' end and are poly-adenylated at the 3' end.The primary miRNAs are subsequently processed in the nucleus by Drosha to form shorter stem loop structures called pre curser-miRNAs or pre-miRNA (figure 2).These pre-miRNAs are then HSOA Journal of Genetics & Genomic Sciences Mini ReviewAbstract microRNAs (miRNAs) are small non-coding single-stranded molecules (containing about 22 nucleotides) that are widely found in many organisms, as varied as micro-organisms, plants, invertebrates and vertebrates. These miRNAs function in RNA silencing and post-transcriptional regulation of gene expression. miRNAs have been found to be involved in a number of biological and pathological processes, including sperm biology and infertility. This review will describe and discuss the role of miRNAs in terms of their role in sperm function, male infertility and gene regulation. a) The fertilising sperm introduces more than the paternal genome, the oocyte-activating factor (PLCζ), proteins from post-acrosomal, and perinuclear thecal proteins and centrioles; b) Sperm also contain a complex population of RNA, ...

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Section: Sperm Mirna and Transgenerational Inheritancementioning

confidence: 97%

Sperm-Specific MicroRNAs - Their Role and Function

Al-Gazi¹,

Carroll²

2016

GGS

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“…R132 L Wang and C Xu vital for healthy sperm and normal embryonic development, particularly in cell death (Marczylo et al 2012). Epigenetics can also affect miRNA expression through DNA methylation and histone modifications and can inversely regulate epigenetic inheritance through DNA methylation transferase, thereby maintaining DNA methylation levels and altering histone modifications (Sato et al 2011, Liu et al 2013a, Udali et al 2013, Nana-Sinkam & Choi 2014.…”

Section: Epigenetics Of Mirna In Spermatogenesis and Tgctsmentioning

confidence: 99%

Role of microRNAs in mammalian spermatogenesis and testicular germ cell tumors

Wang¹,

Xu²

2015

Reproduction

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microRNAs (miRNAs) are a class of small endogenous RNAs, 19-25 nucleotides in size, which play a role in the regulation of gene expression at transcriptional and post-transcriptional levels. Spermatogenesis is a complex process through which spermatogonial stem cells (SSCs) proliferate and differentiate into mature spermatozoa. A large number of miRNAs are abundantly expressed in spermatogenic cells. Growing evidence supports the essential role of miRNA regulation in normal spermatogenesis and male fertility and cumulative research has shown that this form of regulation contributes to the etiology of testicular germ cell tumors (TGCTs). In this review, we addressed recent advancements of miRNA expression profiles in testis and focused on the regulatory functions of miRNA in the process of SSC renewal, spermatogonial mitosis, spermatocyte meiosis, spermiogenesis, and the occurrence of TGCTs.

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“…Increasingly, the potential use of miRNAs as biomarkers is being investigated since they are secreted in multiple body fluids (including blood, semen, saliva), and they are stable (secreted within exosomes), accessible, and easily measured (Gant et al 2015). Spermatozoal miRNAs are of particular interest for regulatory purposes since they can be altered by environmental exposures, transmitted across generations, involved in the physiological or pathophysiological development of subsequent progeny and are easily collected and analysed (Liu et al 2012;Marczylo et al 2012;Rodgers et al 2013Rodgers et al , 2015Gapp et al 2014;Stowe et al 2014). To be used as biomarkers, ncRNAs should further be sensitive, specific, and linearly related to exposure and effect.…”

Section: Expression Of Macroscopicmentioning

confidence: 99%

Advancing the use of noncoding RNA in regulatory toxicology: Report of an ECETOC workshop

Aigner¹,

Buesen²,

Gant³

et al. 2016

Regulatory Toxicology and Pharmacology

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The European Centre for the Ecotoxicology and Toxicology of Chemicals (ECETOC) organised a workshop to discuss the state-of-the-art research on noncoding RNAs (ncRNAs) as biomarkers in regulatory toxicology and as analytical and therapeutic agents. There was agreement that the abundance of data obtained from ncRNA expression profiling requires careful evaluation to determine the utility of specific ncRNAs for regulatory toxicology. To advance the use of ncRNA in regulatory toxicology, the following research priorities were identified: (1) Conduct comprehensive literature reviews to identify candidate ncRNAs for further assessment as potential biomarkers of toxicity and areas of toxicology where ncRNA expression profiling can address prevailing scientific deficiencies.(2) Develop consensus on how to conduct and report ncRNA expression profiling in a toxicological context to support applicability for regulatory decision-making. (3) Conduct experimental projects to evaluate the toxicological relevance of the expression profiles of selected ncRNAs. As necessary, retrospective analyses (e.g. from surplus samples from control groups from regulatory studies) can be supplemented with new (90-day) rat oral toxicity studies. These projects should aim at establishing physiological ncRNA expression profiles including the biological variability of healthy individuals. To substantiate the relevance of key ncRNAs for cell homeostasis or pathogenesis, molecular events should be linked with substance-induced apical effects in a dose-dependent manner. Applying a holistic approach, knowledge on ncRNAs, and relevant information from 'omics and epigenetics technologies, should be integrated into adverse outcome pathways to improve the understanding of the functional roles of ncRNAs within a regulatory context.

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Smoking induces differential miRNA expression in human spermatozoa: A potential transgenerational epigenetic concern?

Cited by 202 publications

References 52 publications

Sperm-Specific MicroRNAs - Their Role and Function

Sperm-Specific MicroRNAs - Their Role and Function

Role of microRNAs in mammalian spermatogenesis and testicular germ cell tumors

Advancing the use of noncoding RNA in regulatory toxicology: Report of an ECETOC workshop

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