scholarly journals MicroRNA-202 (miR-202) controls female fecundity by regulating medaka oogenesis

2018 ◽  
Author(s):  
Stéphanie Gay ◽  
Jérôme Bugeon ◽  
Amine Bouchareb ◽  
Laure Henry ◽  
Jérôme Montfort ◽  
...  
Keyword(s):  
Reproductive Success ◽  
Egg Production ◽  
Biological Processes ◽  
Female Reproduction ◽  
Female Fecundity ◽  
Animal Reproduction ◽  
Non Coding Rnas

ABSTRACTFemale gamete production relies on coordinated molecular and cellular processes that occur in the ovary throughout oogenesis. In fish, as in other vertebrates, these processes have been extensively studied both in terms of endocrine/paracrine regulation and protein expression and activity. The role of small non-coding RNAs in the regulation of animal reproduction remains however largely unknown and poorly investigated, despite a growing interest for the importance of miRNAs in a wide variety of biological processes. Here, we analyzed the role of miR-202, a miRNA predominantly expressed in male and female gonads in several vertebrate species. We studied its expression in the medaka ovary and generated a mutant line (using CRISPR/Cas9 genome engineering) to determine its importance for reproductive success with special interest for egg production. Our results show that miR-202-5p is the biologically active form of the miRNA and that it is expressed in granulosa cells and in the unfertilized egg. The knock out (KO) of miR-202 resulted in a strong phenotype both in terms of number and quality of eggs produced. Mutant females exhibited either no egg production or produced a drastically reduced number of eggs that could not be fertilized, ultimately leading to no reproductive success. We quantified the size distribution of the oocytes in the ovary of KO females and performed a genome-wide transcriptomic analysis approach to identified dysregulated molecular pathways. Together, cellular and molecular analyses indicate that lack of miR-202 impairs the early steps of oogenesis/folliculogenesis and decreases the number of large (i.e. vitellogenic) follicles, ultimately leading to dramatically reduced female fecundity. This study sheds new light on the regulatory mechanisms that control the early steps of follicular development and provides the first in vivo functional evidence that an ovarian-predominant microRNA may have a major role in female reproduction.Author summaryThe role of small non-coding RNAs in the regulation of animal reproduction remains poorly investigated, despite a growing interest for the importance of miRNAs in a wide variety of biological processes. Here, we analyzed the role of miR-202, a miRNA predominantly expressed in gonads in vertebrate. We studied its expression in the medaka ovary and knocked out the miR-202 genes to study its importance for reproductive success. We showed that the lack of miR-202 results in the sterility of both females and males. In particular, it lead to a drastic reduction of both the number and the quality of eggs produced by females. Mutant females exhibited either no egg production or produced a drastically reduced number of eggs that could not be fertilized, ultimately leading to no reproductive success. Quantitative histological and molecular analyses indicated that miR-202 KO impairs oocyte development and is also associated with the dysregulation of many genes that are critical for reproduction. This study sheds new light on the regulatory mechanisms that control oogenesis and provides the first in vivo functional evidence that an ovarian-predominant microRNA may have a major role in female reproduction.

scholarly journals Recent advances in understanding the role of FOXO3

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1372 ◽  
Author(s):  
Renae J. Stefanetti ◽  
Sarah Voisin ◽  
Aaron Russell ◽  
Séverine Lamon
Keyword(s):  
Cell Cycle ◽  
Skeletal Muscle ◽  
Protein Turnover ◽  
Genetic Basis ◽  
The Body ◽  
Biological Processes ◽  
Forkhead Box ◽  
Protein Pool

The forkhead box O3 (FOXO3, or FKHRL1) protein is a member of the FOXO subclass of transcription factors. FOXO proteins were originally identified as regulators of insulin-related genes; however, they are now established regulators of genes involved in vital biological processes, including substrate metabolism, protein turnover, cell survival, and cell death. FOXO3 is one of the rare genes that have been consistently linked to longevity in in vivo models. This review provides an update of the most recent research pertaining to the role of FOXO3 in (i) the regulation of protein turnover in skeletal muscle, the largest protein pool of the body, and (ii) the genetic basis of longevity. Finally, it examines (iii) the role of microRNAs in the regulation of FOXO3 and its impact on the regulation of the cell cycle.

The Salivary miRNome: A Promising Biomarker of Disease

MicroRNA ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Sara Tomei ◽  
Harshitha Shobha Manjunath ◽  
Selvasankar Murugesan ◽  
Souhaila Al Khodor
Keyword(s):  
Current Knowledge ◽  
Transcriptional Level ◽  
Biological Processes ◽  
Circulating Mirnas ◽  
Disease Pathogenesis ◽  
Technical Aspects ◽  
Recent Developments ◽  
Health And Disease ◽  
Non Coding Rnas

: MicroRNAs (miRNAs) are non-coding RNAs ranging from 18-24 nucleotides also known to regulate the human genome mainly at the post-transcriptional level. MiRNAs were shown to play an important role in most biological processes such as apoptosis and in the pathogenesis of many diseases such as cardiovascular diseases and cancer. Recent developments of advanced molecular high-throughput technologies have enhanced our knowledge of miRNAs. MiRNAs can now be discovered, interrogated, and quantified in various body fluids, and hence can serve as diagnostic and therapeutic markers for many diseases. While most studies use blood as a sample source to measure circulating miRNAs as possible biomarkers for disease pathogenesis, fewer studies have assessed the role of salivary miRNAs in health and disease. This review aims at providing an overview of the current knowledge of the salivary miRNome, addressing the technical aspects of saliva sampling and highlighting the applicability of miRNA screening to clinical practice.

scholarly journals Idiopathic Pulmonary Fibrosis: Pathogenesis and the Emerging Role of Long Non-Coding RNAs

2020 ◽  
Vol 21 (2) ◽  
pp. 524 ◽  
Author(s):  
Marina R. Hadjicharalambous ◽  
Mark A. Lindsay
Keyword(s):  
Chronic Disease ◽  
Epithelial Cell ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cell Activation ◽  
Lung Fibroblast ◽  
Biological Processes ◽  
Aberrant Expression ◽  
Non Coding Rnas

Idiopathic pulmonary fibrosis (IPF) is a progressive chronic disease characterized by excessing scarring of the lungs leading to irreversible decline in lung function. The aetiology and pathogenesis of the disease are still unclear, although lung fibroblast and epithelial cell activation, as well as the secretion of fibrotic and inflammatory mediators, have been strongly associated with the development and progression of IPF. Significantly, long non-coding RNAs (lncRNAs) are emerging as modulators of multiple biological processes, although their function and mechanism of action in IPF is poorly understood. LncRNAs have been shown to be important regulators of several diseases and their aberrant expression has been linked to the pathophysiology of fibrosis including IPF. This review will provide an overview of this emerging role of lncRNAs in the development of IPF.

scholarly journals Antioxidant Therapy in Graves’ Orbitopathy

2020 ◽  
Vol 11 ◽  
Author(s):  
Giulia Lanzolla ◽  
Claudio Marcocci ◽  
Michele Marinò
Keyword(s):  
Ros Generation ◽  
Related Condition ◽  
Orbital Radiotherapy ◽  
Antioxidant Agents ◽  
Graves Orbitopathy ◽  
High Doses

The balance of the cell redox state is a key point for the maintenance of cellular homeostasis. Increased reactive oxygen species (ROS) generation leads to oxidative damage of tissues, which is involved in the development of several diseases, including autoimmune diseases. Graves’ Orbitopathy (GO) is a disfiguring autoimmune-related condition associated with Graves’ Disease (GD). Patients with active, moderate-to-severe GO, are generally treated with high doses intravenous glucocorticoids (ivGCs) and/or orbital radiotherapy. On the contrary, up to recently, local ointments were the treatment most frequently offered to patients with mild GO, because the risks related to ivGCs does not justify the relatively poor benefits expected in mild GO. However, a medical treatment for these patients is heavily wanted, considering that GO can progress into more severe forms and also patients with mild GO complain with an impairment in their quality of life. Thus, based on the role of oxidative stress in the pathogenesis of GO, a therapy with antioxidant agents has been proposed and a number of studies have been performed, both in vitro and in vivo, which is reviewed here.

scholarly journals Discovery of methylfarnesoate as the annelid brain hormone reveals an ancient role of sesquiterpenoids in reproduction

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Sven Schenk ◽  
Christian Krauditsch ◽  
Peter Frühauf ◽  
Christopher Gerner ◽  
Florian Raible
Keyword(s):  
Egg Production ◽  
Target Species ◽  
Hormone Activity ◽  
Transcript Levels ◽  
Reproductive Maturation ◽  
Central Energy ◽  
Molecular Signals ◽  
Bristle Worms

Animals require molecular signals to determine when to divert resources from somatic functions to reproduction. This decision is vital in animals that reproduce in an all-or-nothing mode, such as bristle worms: females committed to reproduction spend roughly half their body mass for yolk and egg production; following mass spawning, the parents die. An enigmatic brain hormone activity suppresses reproduction. We now identify this hormone as the sesquiterpenoid methylfarnesoate. Methylfarnesoate suppresses transcript levels of the yolk precursor Vitellogenin both in cell culture and in vivo, directly inhibiting a central energy–costly step of reproductive maturation. We reveal that contrary to common assumptions, sesquiterpenoids are ancient animal hormones present in marine and terrestrial lophotrochozoans. In turn, insecticides targeting this pathway suppress vitellogenesis in cultured worm cells. These findings challenge current views of animal hormone evolution, and indicate that non-target species and marine ecosystems are susceptible to commonly used insect larvicides.

scholarly journals Targeting Wnt/β-Catenin Pathway for Developing Therapies for Hair Loss

2020 ◽  
Vol 21 (14) ◽  
pp. 4915 ◽  
Author(s):  
Bu Young Choi
Keyword(s):  
Hair Loss ◽  
Hair Growth ◽  
In Vivo Studies ◽  
Intracellular Targets ◽  
Remarkable Progress ◽  
Made In

Persistent hair loss is a major cause of psychological distress and compromised quality of life in millions of people worldwide. Remarkable progress has been made in understanding the molecular basis of hair loss and identifying valid intracellular targets for designing effective therapies for hair loss treatment. Whereas a variety of growth factors and signaling pathways have been implicated in hair cycling process, the activation of Wnt/β-catenin signaling plays a central role in hair follicle regeneration. Several plant-derived chemicals have been reported to promote hair growth by activating Wnt/β-catenin signaling in various in vitro and in vivo studies. This mini-review sheds light on the role of Wnt/β-catenin in promoting hair growth and the current progress in designing hair loss therapies by targeting this signaling pathway.

scholarly journals The balancing act of R-loop biology: The good, the bad, and the ugly

2019 ◽  
Vol 295 (4) ◽  
pp. 905-913 ◽  
Author(s):  
Youssef A. Hegazy ◽  
Chrishan M. Fernando ◽  
Elizabeth J. Tran
Keyword(s):  
Genome Instability ◽  
Strand Break ◽  
Biological Processes ◽  
Physiological Importance ◽  
Future Goals ◽  
Dna Double Strand Break ◽  
Positive Functions ◽  
Acid Structure

An R-loop is a three-stranded nucleic acid structure that consists of a DNA:RNA hybrid and a displaced strand of DNA. R-loops occur frequently in genomes and have significant physiological importance. They play vital roles in regulating gene expression, DNA replication, and DNA and histone modifications. Several studies have uncovered that R-loops contribute to fundamental biological processes in various organisms. Paradoxically, although they do play essential positive functions required for important biological processes, they can also contribute to DNA damage and genome instability. Recent evidence suggests that R-loops are involved in a number of human diseases, including neurological disorders, cancer, and autoimmune diseases. This review focuses on the molecular basis for R-loop–mediated gene regulation and genomic instability and briefly discusses methods for identifying R-loops in vivo. It also highlights recent studies indicating the role of R-loops in DNA double-strand break repair with an updated view of much-needed future goals in R-loop biology.

Anchoring of FLT3 in the endoplasmic reticulum alters signaling quality

Blood ◽  
2009 ◽  
Vol 113 (15) ◽  
pp. 3568-3576 ◽  
Author(s):  
Dirk Schmidt-Arras ◽  
Sylvia-Annette Böhmer ◽  
Sina Koch ◽  
Jörg P. Müller ◽  
Lutz Blei ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Transformation ◽  
Intracellular Location ◽  
Er Retention ◽  
Transforming Activity ◽  
Signaling Quality

Abstract The mechanism of cell transformation by Fms-like tyrosine kinase 3 (FLT3) in acute myeloid leukemia (AML) is incompletely understood. The most prevalent activated mutant FLT3 ITD exhibits an altered signaling quality, including strong activation of the STAT5 transcription factor. FLT3 ITD has also been found partially retained as a high-mannose precursor in an intracellular compartment. To analyze the role of intracellular retention of FLT3 for transformation, we have generated FLT3 versions that are anchored in the perinuclear endoplasmic reticulum (ER) by appending an ER retention sequence containing a RRR (R3) motif. ER retention of R3, but not of corresponding A3 FLT3 versions, is shown by biochemical, fluorescence-activated cell sorting, and immunocytochemical analyses. ER anchoring reduced global autophosphorylation and diminished constitutive activation of ERK1/2 and AKT of the constitutively active FLT3 versions. ER anchoring was, however, associated with elevated signaling to STAT3. Transforming activity of the FLT3 D835Y mutant was suppressed by ER anchoring. In contrast, ER-anchored FLT3 ITD retained STAT5-activating capacity and was transforming in vitro and in vivo. The findings highlight another aspect of the different signaling quality of FLT3 ITD: It can transform cells from an intracellular location.

ceRNAs and ceRNA Networks in Normal and Malignant Hematopoiesis and Their Therapeutic Implications

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. SCI-30-SCI-30
Author(s):  
Pier Paolo Pandolfi
Keyword(s):  
Cross Talk ◽  
Conflicts Of Interest ◽  
Therapeutic Implications ◽  
Hematopoietic Malignancies ◽  
Competing Endogenous Rnas ◽  
Non Coding Rnas

Abstract We will discuss exciting new data regarding the role of pseudogenes, long intergenic non-coding RNAs (lincRNAs) and miRNAs in the pathogenesis of leukemia and lymphoma, as also studied in vivo in the mouse, and their therapeutic implications. We will also focus on competing endogenous RNAs (ceRNAs), circular(circ)-ceRNAs and pseudo-ceRNAs and give important attention to how understanding their cross-talk and the ceRNA language will facilitate efforts to deconvolute ceRNA networks and their role in the pathogenesis of hematopoietic malignancies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Applications of Melatonin in Female Reproduction in the Context of Oxidative Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yonghui Jiang ◽  
Huangcong Shi ◽  
Yue Liu ◽  
Shigang Zhao ◽  
Han Zhao
Keyword(s):  
Oxidative Stress ◽  
Polycystic Ovary ◽  
Oocyte Quality ◽  
Early Embryo ◽  
Female Reproduction ◽  
Adverse Conditions ◽  
Wide Range

Oxidative stress has been recognized as one of the causal mediators of female infertility by affecting the oocyte quality and early embryo development. Improving oxidative stress is essential for reproductive health. Melatonin, a self-secreted antioxidant, has a wide range of effects by improving mitochondrial function and reducing the damage of reactive oxygen species (ROS). This minireview illustrates the applications of melatonin in reproduction from four aspects: physiological ovarian aging, vitrification freezing, in vitro maturation (IVM), and oxidative stress homeostasis imbalance associated with polycystic ovary syndrome (PCOS), emphasising the role of melatonin in improving the quality of oocytes in assisted reproduction and other adverse conditions.

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