Arrdc4‐dependent extracellular vesicle biogenesis is required for sperm maturation

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dc.contributor.authorFoot, N.J.
dc.contributor.authorGonzalez, M.B.
dc.contributor.authorGembus, K.
dc.contributor.authorFonseka, P.
dc.contributor.authorSandow, J.J.
dc.contributor.authorNguyen, T.T.
dc.contributor.authorTran, N.
dc.contributor.authorWebb, A.I.
dc.contributor.authorMathivanan, S.
dc.contributor.authorRobker, R.L.
dc.contributor.authorKumar, S.
dc.date.issued2021
dc.description.abstractExtracellular vesicles (EVs) are important players in cell to cell communication in reproductive systems. Notably, EVs have been found and characterized in the male reproductive tract, however, direct functional evidence for their importance in mediating sperm function is lacking. We have previously demonstrated that Arrdc4, a member of the α-arrestin protein family, is involved in extracellular vesicle biogenesis and release. Here we show that Arrdc4-mediated extracellular vesicle biogenesis is required for proper sperm function. Sperm from Arrdc4–/– mice develop normally through the testis but fail to acquire adequatemotility and fertilization capabilities through the epididymis, as observed by reduced motility, premature acrosome reaction, reduction in zona pellucida binding and two-cell embryo production. We found a significant reduction in extracellular vesicle production by Arrdc4–/- epididymal epithelial cells, and further, supplementation of Arrdc4–/– sperm with additional vesicles dampened the acrosome reaction defect and restored zona pellucida binding. These results indicate that Arrdc4 is important for proper spermmaturation through the control of extracellular vesicle biogenesis.
dc.description.statementofresponsibilityNatalie J. Foot, Macarena B. Gonzalez, Kelly Gembus, Pamali Fonseka, Jarrod J. Sandow, Thuy Tien Nguyen, Diana Tran, Andrew I. Webb, Suresh Mathivanan, Rebecca L. Robker, Sharad Kumar
dc.identifier.citationJournal of Extracellular Vesicles, 2021; 10(8):e12113-1-e12113-21
dc.identifier.doi10.1002/jev2.12113
dc.identifier.issn2001-3078
dc.identifier.issn2001-3078
dc.identifier.orcidFoot, N.J. [0000-0002-6567-9283]
dc.identifier.orcidTran, N. [0000-0002-4023-3373]
dc.identifier.orcidRobker, R.L. [0000-0002-1538-4604]
dc.identifier.orcidKumar, S. [0000-0001-7126-9814]
dc.identifier.urihttps://hdl.handle.net/2440/146566
dc.language.isoen
dc.publisherWiley
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/GNT1122437
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/GNT1103006
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/GNT1117976
dc.rights© 2021 TheAuthors. Journal of Extracellular Vesicles published byWiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
dc.source.urihttps://doi.org/10.1002/jev2.12113
dc.subjectarrestin; biogenesis; extracellular vesicles; fertility; sperm maturation; ubiquitin ligase adaptors
dc.subject.meshTestis
dc.subject.meshEpididymis
dc.subject.meshZona Pellucida
dc.subject.meshSpermatozoa
dc.subject.meshAcrosome
dc.subject.meshAnimals
dc.subject.meshMice, Inbred C57BL
dc.subject.meshMice, Inbred CBA
dc.subject.meshMice
dc.subject.meshIntracellular Signaling Peptides and Proteins
dc.subject.meshSperm Maturation
dc.subject.meshSperm-Ovum Interactions
dc.subject.meshAcrosome Reaction
dc.subject.meshFemale
dc.subject.meshMale
dc.subject.meshExtracellular Vesicles
dc.titleArrdc4‐dependent extracellular vesicle biogenesis is required for sperm maturation
dc.typeJournal article
pubs.publication-statusPublished

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