Small RNAs in early mammalian development: From gametes to gastrulation

The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, and Department of Urology, University of California San Francisco, San Francisco, CA 94143, USA.
Development (Impact Factor: 6.46). 05/2011; 138(9):1653-61. DOI: 10.1242/dev.056234
Source: PubMed


Small non-coding RNAs, including microRNAs (miRNAs), endogenous small interfering RNAs (endo-siRNAs) and Piwi-interacting RNAs (piRNAs), play essential roles in mammalian development. The function and timing of expression of these three classes of small RNAs differ greatly. piRNAs are expressed and play a crucial role during male gametogenesis, whereas endo-siRNAs are essential for oocyte meiosis. By contrast, miRNAs are ubiquitously expressed in somatic tissues and function throughout post-implantation development. Surprisingly, however, miRNAs are non-essential during pre-implantation embryonic development and their function is suppressed during oocyte meiosis. Here, we review the roles of small non-coding RNAs during the early stages of mammalian development, from gamete maturation through to gastrulation.

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    • "DROSHA is responsible for the processing of miRNA primary transcripts into precursor miRNAs (pre-miRNAs) in the nucleus, whereas DICER cleaves the pre-miRNAs into mature miRNAs in the cytoplasm. The miRNA production requires both RNase III enzymes, Development • Advance article whereas endo-siRNA production only needs DICER (Lee et al., 2006; Suh and Blelloch, 2011; Yang and Lai, 2011). By generating male germline-specific Dicer or Drosha conditional KO mice, we have demonstrated that these cKO male mice produce a small number of normal-looking sperm despite low sperm counts and reduced motility (Wu et al., 2012). "
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    ABSTRACT: Although it is believed that mammalian sperm carry small noncoding RNAs (sncRNAs) into oocytes during fertilization, it remains unknown whether these sperm-borne sncRNAs truly have any function during fertilization and preimplantation embryonic development. Germline-specific Dicer and Drosha conditional knockout (cKO) mice produce gametes (i.e., sperm and oocytes) partially deficient in miRNAs and/or endo-siRNAs, thus providing a unique opportunity for testing whether normal sperm (paternal) or oocyte (maternal) miRNA and endo-siRNA contents are required for fertilization and preimplantation development. Using the outcome of intracytoplasmic sperm injection (ICSI) as a readout, we found that sperm with altered miRNA and endo-siRNA profiles could fertilize wild-type (WT) eggs, but embryos derived from these partially sncRNA-deficient sperm displayed a significant reduction in developmental potential, which could be rescued by injecting WT sperm-derived total or small RNAs into ICSI embryos. Disrupted maternal transcript turnover and failure in early zygotic gene activation appeared to associate with the aberrant miRNA profiles in Dicer and Drosha cKO spermatozoa. Overall, our data support a critical function of paternal miRNAs and/or endo-siRNAs in the control of the transcriptomic homeostasis in fertilized eggs, zygotes and 2-cell embryos. Given that supplementation of sperm RNAs enhances both the developmental potential of preimplantation embryos and the live birth rate, it may represent a novel means to improve the success rate of assisted reproductive technologies in fertility clinics.
    Full-text · Article · Dec 2015 · Development
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    • "The transcriptome of these oocytes is widely perturbed and expression of the most abundant transposable element in mouse oocytes is increased (Stein et al. 2015). It is believed that, after fertilization, neither miRNAs nor siRNAs play a role in preimplantation development, since zygotic deletions of Dgcr8, Dicer, and Ago2 do not have a phenotype until after embryo implantation (Bernstein et al. 2003; Morita et al. 2007; Suh and Blelloch 2011). Moreover, maternal deletion of Dgcr8 has no phenotype until postimplantation , suggesting no essential role for maternal miRNAs throughout oocyte maturation or during the whole preimplantation development (Suh et al. 2010). "
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    ABSTRACT: A hallmark of oocyte development in mammals is the dependence on the translation and utilization of stored RNA and proteins rather than the de novo transcription of genes in order to sustain meiotic progression and early embryo development. In the absence of transcription, the completion of meiosis and early embryo development in mammals relies significantly on maternally synthesized RNAs. Post-transcriptional control of gene expression at the translational level has emerged as an important cellular function in normal development. Therefore, the regulation of gene expression in oocytes is controlled almost exclusively at the level of mRNA and protein stabilization and protein synthesis. This current review is focused on the recently emerged findings on RNA distribution related to the temporal and spatial translational control of the meiotic progression of the mammalian oocyte.
    Full-text · Article · Sep 2015 · Cell and Tissue Research
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    • "Oocytes contain large amounts of RNA of all classes (Watanabe et al., 2006, 2008; Tam et al., 2008). Previous studies have demonstrated that maternal non-coding RNAs can be stable for several cell divisions and contribute to gene regulation in early development (Suh and Blelloch, 2011). In contrast, spermatozoa have a highly condensed nucleus, are transcriptionally nearly silent and contain little cytoplasm. "
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    ABSTRACT: BACKGROUND Traditional studies focused on DNA as the heritable information carrier that passes the phenotype from parents to offspring. However, increasing evidence suggests that information, that is independent of the DNA sequence, termed epigenetic information, can be inherited between generations. Recently, in our lab, we found that prediabetes in fathers increases the susceptibility to diabetes in offspring through gametic cytosine methylation changes. Paternal prediabetes changed overall methylation patterns in sperm, and a large portion of differentially methylated loci can be transmitted to pancreatic islets of offspring up to the second generation. In this review, we survey the extensive examples of environmentally induced epigenetic inheritance in various species, ranging from Caenorhabditis elegans to humans. We focus mainly on elucidating the molecular basis of environmental epigenetic inheritance through gametes, which is an emerging theme and has important implications for explaining the prevalence of obesity, type 2 diabetes and other chronic non-genetic diseases, which is also important for understanding the influence of environmental exposures on reproductive and overall health in offspring.
    Preview · Article · Nov 2014 · Human Reproduction Update
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