The Role of the Epididymis and the Contribution of Epididymosomes to Mammalian Reproduction

James, Emma; Carrell, Douglas T.; Aston, Kenneth I.; Jenkins, Timothy G.; Yeste, Marc; Salas‐Huetos, Albert

doi:10.3390/ijms21155377

Cited by 150 publications

(109 citation statements)

References 88 publications

(190 reference statements)

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“…While the identity of these vesicles was not tested, we hypothesise that they are epididymis-derived exosomes, known as epididymosomes, in the process of fusing with the sperm. This process is known to be critical for sperm function, but it is still poorly understood (22, 23). The distinct alignment of these structures along the equatorial segment (which corresponds to the site of sperm-oocyte fusion (24)), and the head-tail-coupling apparatus (at the junction of the sperm head and tail), is supportive of the targeted transport of molecules from epididymal epithelial cells to the transcriptionally and translationally silent sperm to modify sperm function via a broad set of processes collectively known as epididymal maturation.…”

Section: Resultsmentioning

confidence: 99%

New insights into sperm ultrastructure through enhanced scanning electron microscopy

Korneev

Merriner

Gervinskas

et al. 2020

Preprint

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The analysis of spermatozoa morphology is fundamental to understand male fertility and the aetiology of infertility. Traditionally scanning electron microscopy (SEM) has been used to define surface topology. Recently, however, it has become a critical tool for three-dimensionally analyse of internal cellular ultrastructure. Modern SEM provides nanometer-scale resolution, but the meaningfulness of such information is proportional to the quality of the sample preservation. In this study, we demonstrate that sperm quickly and robustly adhere to gold-coated surfaces. Leveraging this property, we developed three step-by-step protocols fulfilling different needs for sperm imaging: chemically fixed monolayers for SEM examination of the external morphology, and two high-pressure freezing-based protocols for fast SEM examination of full cell internal morphology and focused ion-beam SEM (FIB-SEM) tomography. These analyses allow previously unappreciated insights into mouse sperm ultrastructure, including the identification of novel structures within the fibrous sheath and domain-specific interactions between the plasma membrane and exosome-like structures.

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Section: Resultsmentioning

confidence: 99%

New insights into sperm ultrastructure through enhanced scanning electron microscopy

Korneev

Merriner

Gervinskas

et al. 2020

Preprint

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“…One possible explanation is that fluid retention and back pressure, caused by ED obstructions, may contribute to the sperm morphological defects. Alternatively, it could be attributable to changes in the luminal microenvironment of the epididymis as testicular sperm undergo complex maturation processes as they travel through the epididymis [47][48][49].…”

Section: Discussionmentioning

confidence: 99%

The Distal Appendage Protein CEP164 Is Essential for Efferent Duct Multiciliogenesis and Male Fertility

Hoque

Chen

Hess

et al. 2020

Preprint

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Cilia are evolutionarily conserved microtubule-based structures that perform diverse biological functions. Cilia are assembled on basal bodies and anchored to the plasma membrane via distal appendages. Multiciliated cells (MCCs) are a specialized cell type with hundreds of motile multicilia, lining the brain ventricles, airways, and reproductive tracts to propel fluids/substances across the epithelial surface. In the male reproductive tract, MCCs in efferent ducts (EDs) move in a whip-like motion to stir the luminal contents and prevent sperm agglutination. Previously, we demonstrated that the essential distal appendage protein CEP164 recruits Chibby1 (Cby1), a small coiled-coil-containing protein, to basal bodies to facilitate basal body docking and ciliogenesis. Mice lacking CEP164 in MCCs (FoxJ1-Cre;CEP164fl/fl) show a significant loss of multicilia in the trachea, oviduct, and ependyma. In addition, we observed male sterility, however, the precise role of CEP164 in male fertility remained unknown. Here, we report that the seminiferous tubules and rete testis of FoxJ1-Cre;CEP164fl/fl mice exhibit substantial dilation, indicative of dysfunctional multicilia in the EDs. Consistent with these findings, multicilia were hardly detectable in the EDs of FoxJ1-Cre;CEP164fl/fl mice although FoxJ1-positive immature cells were present. Sperm aggregation and agglutination were commonly noticeable in the lumen of the seminiferous tubules and EDs of FoxJ1-Cre;CEP164fl/fl mice. In FoxJ1-Cre;CEP164fl/fl mice, the apical localization of Cby1 and the transition zone marker NPHP1 was severely diminished, suggesting basal body docking defects. TEM analysis of EDs further confirmed basal body accumulation in the cytoplasm of MCCs. Collectively, we conclude that deletion of CEP164 in the MCCs of EDs causes basal body docking defects and loss of multicilia, leading to sperm agglutination, obstruction of EDs, and male infertility. Our study therefore unravels an essential role of the distal appendage protein CEP164 in male fertility.Author SummaryMulticilia are tinny hair-like microtubule-based structures that beat in a whip-like pattern to generate a fluid flow on the apical cell surface. Multiciliated cells are essential for the proper function of major organs such as brain, airway, and reproductive tracts. In the male reproductive system, multiciliated cells are present in the efferent ducts, which are small tubules that connect the testis to the epididymis. However, the importance of multiciliated cells in male fertility remains poorly understood. Here, we investigated the role of the critical ciliary protein CEP164 in male fertility using a mouse model lacking CEP164 in multiciliated cells. Male mice are infertile with reduced sperm counts. We demonstrate that, in the absence of CEP164, multiciliated cells are present in the efferent ducts but fail to extend multicilia due to basal body docking defects. Consistent with this, the recruitment of key ciliary proteins is perturbed. As a result, these mice show sperm agglutination, obstruction of sperm transport, and degeneration of germ cells in the testis, leading to infertility. Our study therefore reveals essential roles of CEP164 in the formation of multicilia in the efferent ducts and male fertility.

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“…While the identity of these vesicles was not tested, we hypothesize that they are epididymis-derived exosomes, known as epididymosomes, in the process of fusing with the sperm. This process is known to be critical for sperm function, but it is still poorly understood (Trigg et al, 2019;James et al, 2020). The distinct alignment of these structures along the equatorial segment [which corresponds to the site of sperm-oocyte fusion (Muro and Okabe, 2011)], and the head-tail-coupling apparatus (at the junction of the sperm head and tail), is supportive of the targeted transport of molecules from epididymal epithelial cells to the transcriptionally and translationally silent sperm to modify sperm function via a broad set of processes collectively known as epididymal maturation.…”

Section: External Sperm Morphologymentioning

confidence: 99%

New Insights Into Sperm Ultrastructure Through Enhanced Scanning Electron Microscopy

Korneev

Merriner

Gervinskas

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The analysis of spermatozoa morphology is fundamental to understand male fertility and the etiology of infertility. Traditionally scanning electron microscopy (SEM) has been used to define surface topology. Recently, however, it has become a critical tool for three-dimensional analysis of internal cellular ultrastructure. Modern SEM provides nanometer-scale resolution, but the meaningfulness of such information is proportional to the quality of the sample preservation. In this study, we demonstrate that sperm quickly and robustly adhere to gold-coated surfaces. Leveraging this property, we developed three step-by-step protocols fulfilling different needs for sperm imaging: chemically fixed monolayers for SEM examination of the external morphology, and two high-pressure freezing-based protocols for fast SEM examination of full cell internal morphology and focused ion-beam SEM tomography. These analyses allow previously unappreciated insights into mouse sperm ultrastructure, including the identification of novel structures within the fibrous sheath and domain-specific interactions between the plasma membrane and exosome-like structures.

show abstract

The Role of the Epididymis and the Contribution of Epididymosomes to Mammalian Reproduction

Cited by 150 publications

References 88 publications

New insights into sperm ultrastructure through enhanced scanning electron microscopy

New insights into sperm ultrastructure through enhanced scanning electron microscopy

The Distal Appendage Protein CEP164 Is Essential for Efferent Duct Multiciliogenesis and Male Fertility

New Insights Into Sperm Ultrastructure Through Enhanced Scanning Electron Microscopy

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