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29 July 2017 Dynamic expression of long noncoding RNAs reveals their potential roles in spermatogenesis and fertility
Lauren Wichman, Saigopal Somasundaram, Christine Breindel, Dana M. Valerio, John R. McCarrey, Craig A. Hodges, Ahmad M. Khalil
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Abstract

Mammalian reproduction requires that males and females produce functional haploid germ cells through complex cellular differentiation processes known as spermatogenesis and oogenesis, respectively. While numerous studies have functionally characterized protein-coding genes and small noncoding RNAs (microRNAs and piRNAs) that are essential for gametogenesis, the roles of regulatory long noncoding RNAs (lncRNAs) are yet to be fully characterized. Previously, we and others have demonstrated that intergenic regions of the mammalian genome encode thousands of long noncoding RNAs, and many studies have now demonstrated their critical roles in key biological processes. Thus, we postulated that some lncRNAs may also impact mammalian spermatogenesis and fertility. In this study, we identified a dynamic expression pattern of lncRNAs during murine spermatogenesis. Importantly, we identified a subset of lncRNAs and very few mRNAs that appear to escape meiotic sex chromosome inactivation, an epigenetic process that leads to the silencing of the X- and Y-chromosomes at the pachytene stage of meiosis. Further, some of these lncRNAs and mRNAs show a strong testis expression pattern suggesting that they may play key roles in spermatogenesis. Lastly, we generated a mouse knockout of one X-linked lncRNA, Tslrn1 (testis-specific long noncoding RNA 1), and found that males carrying a Tslrn1 deletion displayed normal fertility but a significant reduction in spermatozoa. Our findings demonstrate that dysregulation of specific mammalian lncRNAs is a novel mechanism of low sperm count or infertility, thus potentially providing new biomarkers and therapeutic strategies.

Summary Sentence

Long non-coding RNAs are critical for mammalian spermatogenesis.

© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Lauren Wichman, Saigopal Somasundaram, Christine Breindel, Dana M. Valerio, John R. McCarrey, Craig A. Hodges, and Ahmad M. Khalil "Dynamic expression of long noncoding RNAs reveals their potential roles in spermatogenesis and fertility," Biology of Reproduction 97(2), 313-323, (29 July 2017). https://doi.org/10.1093/biolre/iox084
Received: 22 February 2017; Accepted: 27 July 2017; Published: 29 July 2017
JOURNAL ARTICLE
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KEYWORDS
CRISPR/Cas9
epigenetics
lncRNAs
meiosis
spermatogenesis
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