1173715_Foot,N_2021.pdf (4.84 MB)
Download fileArrdc4-dependent extracellular vesicle biogenesis is required for sperm maturation
journal contribution
posted on 11.08.2021, 04:01 authored by Natalie J Foot, Macarena B Gonzalez, Kelly Gembus, Hewafonsekage FonsekaHewafonsekage Fonseka, Jarrod J Sandow, Thi Thuy Dung NguyenThi Thuy Dung Nguyen, Diana Tran, Andrew I Webb, Suresh MathivananSuresh Mathivanan, Rebecca L Robker, Sharad KumarExtracellular 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 adequate motility 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 sperm maturation through the control of extracellular vesicle biogenesis.
Funding
NationalHealth andMedical ResearchCouncil, Grant/AwardNumbers: GNT1122437, GNT1103006, GNT1117976
History
Publication Date
01/06/2021Journal
JOURNAL OF EXTRACELLULAR VESICLESVolume
10Issue
8Article Number
ARTN e12113Pagination
21p.Publisher
WILEYISSN
2001-3078Rights Statement
The Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.Publisher DOI
Usage metrics
Categories
Keywords
Science & TechnologyLife Sciences & BiomedicineCell Biologyarrestinbiogenesisextracellular vesiclesfertilitysperm maturationubiquitin ligase adaptorsRICH SECRETORY PROTEINSPLASMA-MEMBRANEMALE-FERTILITYADENOSINE-TRIPHOSPHATASEEPIDIDYMAL TRANSITBETA-DEFENSINMOTILITYARRESTINIDENTIFICATIONUBIQUITINATION