Epididymal protein Rnase10 is required for post‐testicular sperm maturation and male fertility

Krutskikh, Anton; Poliandri, Ariel; Cabrera-Sharp, Victoria; Dacheux, J. L.; Poutanen, Matti; Huhtaniemi, Ilpo

doi:10.1096/fj.12-205211

Cited by 59 publications

(44 citation statements)

References 58 publications

(84 reference statements)

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“…Moreover, mouse Spag11a exhibited a region-specific expression pattern and was mainly present in the caput region. This is similar to several genes that are important for sperm maturation such as Rnase10 [34,35], Crisp4 [36,37], and Crisp1 [17], which are exclusively expressed in the initial segment, caput and corpus/cauda, respectively. This region-specific expression is important to create specific environments for sperm maturation.…”

Section: Discussionmentioning

confidence: 52%

Sperm-associated antigen 11A is expressed exclusively in the principal cells of the mouse caput epididymis in an androgen-dependent manner

Pujianto

Loanda

Sari

et al. 2013

Reprod Biol Endocrinol

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BackgroundEpididymal sperm maturation occurs via interactions between sperm and proteins secreted by the epididymal epithelium. Although this is an important process, the genes that encode the involved proteins remain largely uncharacterized. Previous studies have demonstrated that the genes involved in sperm maturation are regulated by androgen. Spag11a is an epididymal gene that is influenced by androgen. However, little is known about the putative role of this gene in the sperm maturation process. The objective of this study was to characterize Spag11a in the mouse epididymis.MethodsIn silico analyses were performed to predict signal peptides and functional domains. Spag11a expression was measured by quantitative real-time RT-PCR. Western blots and immunocytochemistry were performed to determine protein expression.ResultsSPAG11A is a member of the beta defensin protein family and constitutes a secretory protein. Spag11a was expressed exclusively in the epididymis. Moreover, it exhibited region-specific expression in the caput, which is typical for genes that are involved in creating a suitable microenvironment for sperm maturation. Mouse Spag11a was regulated by androgen. A significant decrease of Spag11a expression was observed at third day following a gonadectomy (P < 0.001). Interestingly, testosterone replacement therapy was able to maintain the expression almost at the normal level, indicating a dependency on androgen. Besides androgen, testicular factors influenced Spag11a expression in a different way. This was revealed by efferent duct ligation in which Spag11a was transiently up-regulated at the third day following the ligation before returning to the normal level at day 5. Spag11a regional expression was also observed at protein level detected by western immunoblotting which revealed a clear band in the caput but not in other regions. The prediction that SPAG11A is a secretory protein was confirmed by immunocytochemical analyses indicating cell-specific expression mainly in the caput principal cells and detection of the protein in epididymal luminal fluid and spermatozoa.ConclusionsBased on the characteristics of Spag11a, it is likely that this gene has a specific role in epididymal sperm maturation. Further studies using functional assays are necessary to confirm this finding.

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Section: Discussionmentioning

confidence: 52%

Sperm-associated antigen 11A is expressed exclusively in the principal cells of the mouse caput epididymis in an androgen-dependent manner

Pujianto

Loanda

Sari

et al. 2013

Reprod Biol Endocrinol

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“…Among all these KO genes in male mice, Adam3 is strongly reduced or incorrectly located on the mature epididymal sperm surface. The loss of ADAM3 from the mature sperm surface was also observed after Rnase10 gene KO, a protein secreted only in the initial segment of the epididymis and without any sperm membrane affinities (Krutskikh et al 2012). Such results show that the stability, integrity, and location of ADAM3 at the sperm surface are linked to the presence and/or activities of several other proteins.…”

Section: Epididymal Surroundings and Sperm Proteins Involved In Egg-bmentioning

confidence: 62%

New insights into epididymal function in relation to sperm maturation

2014

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Testicular spermatozoa acquire fertility only after 1 or 2 weeks of transit through the epididymis. At the end of this several meters long epididymal tubule, the male gamete is able to move, capacitate, migrate through the female tract, bind to the egg membrane and fuse to the oocyte to result in a viable embryo. All these sperm properties are acquired after sequential modifications occurring either at the level of the spermatozoon or in the epididymal surroundings. Over the last few decades, significant increases in the understanding of the composition of the male gamete and its surroundings have resulted from the use of new techniques such as genome sequencing, proteomics combined with high-sensitivity mass spectrometry, and gene-knockout approaches. This review reports and discusses the most relevant new results obtained in different species regarding the various cellular processes occurring at the sperm level, in particular, those related to the development of motility and egg binding during epididymal transit.

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“…Paradoxically the sperm from the mutants are extremely poor at binding firmly to the ZP of eggs, whereas wild-type sperm bind effectively (Figure 4E). Recent studies in the mouse have shown that sperm that have undergone the AR can penetrate an egg, although this was not an efficient process [25], [26] and mouse sperm from several KOs cannot strongly bind to the ZP and yet are still able to fertilize [27], [28].…”

Section: Resultsmentioning

confidence: 99%

Partial Deletion of Chromosome 8 β-defensin Cluster Confers Sperm Dysfunction and Infertility in Male Mice

et al. 2013

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β-defensin peptides are a family of antimicrobial peptides present at mucosal surfaces, with the main site of expression under normal conditions in the male reproductive tract. Although they kill microbes in vitro and interact with immune cells, the precise role of these genes in vivo remains uncertain. We show here that homozygous deletion of a cluster of nine β-defensin genes (DefbΔ9) in the mouse results in male sterility. The sperm derived from the mutants have reduced motility and increased fragility. Epididymal sperm isolated from the cauda should require capacitation to induce the acrosome reaction but sperm from the mutants demonstrate precocious capacitation and increased spontaneous acrosome reaction compared to wild-types but have reduced ability to bind the zona pellucida of oocytes. Ultrastructural examination reveals a defect in microtubule structure of the axoneme with increased disintegration in mutant derived sperm present in the epididymis cauda region, but not in caput region or testes. Consistent with premature acrosome reaction, sperm from mutant animals have significantly increased intracellular calcium content. Thus we demonstrate in vivo that β-defensins are essential for successful sperm maturation, and their disruption leads to alteration in intracellular calcium, inappropriate spontaneous acrosome reaction and profound male infertility.

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Epididymal protein Rnase10 is required for post‐testicular sperm maturation and male fertility

Cited by 59 publications

References 58 publications

Sperm-associated antigen 11A is expressed exclusively in the principal cells of the mouse caput epididymis in an androgen-dependent manner

Sperm-associated antigen 11A is expressed exclusively in the principal cells of the mouse caput epididymis in an androgen-dependent manner

New insights into epididymal function in relation to sperm maturation

Partial Deletion of Chromosome 8 β-defensin Cluster Confers Sperm Dysfunction and Infertility in Male Mice

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