The Role of the Epididymis in Linking the Legacy of Paternal Exposures to Alteration of the Sperm Epigenome

In what has become a well-established paradigm, paternal exposure to a range of environmental stressors is known to elicit distinct changes to the sperm small noncoding RNA (sncRNA) profile; modifications that can have significant post-fertilization consequences. Despite this knowledge, there remain...

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Main Author: Brett NIXON
Format: Article
Language:English
Published: World Scientific Publishing 2022-09-01
Series:Fertility & Reproduction
Online Access:https://www.worldscientific.com/doi/10.1142/S2661318222740267
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author Brett NIXON
author_facet Brett NIXON
author_sort Brett NIXON
collection DOAJ
description In what has become a well-established paradigm, paternal exposure to a range of environmental stressors is known to elicit distinct changes to the sperm small noncoding RNA (sncRNA) profile; modifications that can have significant post-fertilization consequences. Despite this knowledge, there remains limited mechanistic understanding of how paternal exposures modify the sperm sncRNA landscape. To address this question, our laboratory has exploited a tractable exposure model in which male mice were subjected to acute administration of the reproductive toxicant, acrylamide; a challenge that elicited robust changes to their sperm sncRNA profile. Further, we traced the differential accumulation of acrylamide-responsive sncRNAs to coincide with sperm transit of the proximal (caput) segment of the epididymis, wherein acrylamide exposure altered the expression of several transcription factors implicated in the expression of acrylamide-sensitive sncRNAs. We have also identified extracellular vesicles (epididymosomes) secreted from the caput epididymal epithelium in relaying altered sncRNA profiles to maturing spermatozoa, the implications of which manifest in the form of dysregulated gene expression during early embryonic development following fertilization by acrylamide-exposed sperm. Overall, these data provide mechanistic links to account for how environmental insults can alter the sperm epigenome and compromise the transcriptomic profile of early embryos.
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spelling doaj.art-fb2ed4f1617a473b9e88bb4deb6390b02022-12-22T04:11:24ZengWorld Scientific PublishingFertility & Reproduction2661-31822661-31742022-09-010403n0411411410.1142/S2661318222740267The Role of the Epididymis in Linking the Legacy of Paternal Exposures to Alteration of the Sperm EpigenomeBrett NIXON0The University of Newcastle Priority Research Centre for Reproductive Science and the Hunter Medical Research Institute Program in Reproductive Health and Infertility, AustraliaIn what has become a well-established paradigm, paternal exposure to a range of environmental stressors is known to elicit distinct changes to the sperm small noncoding RNA (sncRNA) profile; modifications that can have significant post-fertilization consequences. Despite this knowledge, there remains limited mechanistic understanding of how paternal exposures modify the sperm sncRNA landscape. To address this question, our laboratory has exploited a tractable exposure model in which male mice were subjected to acute administration of the reproductive toxicant, acrylamide; a challenge that elicited robust changes to their sperm sncRNA profile. Further, we traced the differential accumulation of acrylamide-responsive sncRNAs to coincide with sperm transit of the proximal (caput) segment of the epididymis, wherein acrylamide exposure altered the expression of several transcription factors implicated in the expression of acrylamide-sensitive sncRNAs. We have also identified extracellular vesicles (epididymosomes) secreted from the caput epididymal epithelium in relaying altered sncRNA profiles to maturing spermatozoa, the implications of which manifest in the form of dysregulated gene expression during early embryonic development following fertilization by acrylamide-exposed sperm. Overall, these data provide mechanistic links to account for how environmental insults can alter the sperm epigenome and compromise the transcriptomic profile of early embryos.https://www.worldscientific.com/doi/10.1142/S2661318222740267
spellingShingle Brett NIXON
The Role of the Epididymis in Linking the Legacy of Paternal Exposures to Alteration of the Sperm Epigenome
Fertility & Reproduction
title The Role of the Epididymis in Linking the Legacy of Paternal Exposures to Alteration of the Sperm Epigenome
title_full The Role of the Epididymis in Linking the Legacy of Paternal Exposures to Alteration of the Sperm Epigenome
title_fullStr The Role of the Epididymis in Linking the Legacy of Paternal Exposures to Alteration of the Sperm Epigenome
title_full_unstemmed The Role of the Epididymis in Linking the Legacy of Paternal Exposures to Alteration of the Sperm Epigenome
title_short The Role of the Epididymis in Linking the Legacy of Paternal Exposures to Alteration of the Sperm Epigenome
title_sort role of the epididymis in linking the legacy of paternal exposures to alteration of the sperm epigenome
url https://www.worldscientific.com/doi/10.1142/S2661318222740267
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