The blood-epididymis barrier and inflammation

Gregory, Mary; Cyr, Daniel G.

doi:10.4161/21565562.2014.979619

Cited by 65 publications

(55 citation statements)

References 163 publications

(175 reference statements)

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“…The activities encoded by these gene clusters encompass many of the best-characterized functions of the epididymis, as for example glycocalyx and membrane remodeling of the sperm surface is one of the first processes identified to occur in this tissue (Tecle and Gagneux, 2015), while the wide array of antimicrobial peptides presumably serve to insulate the testis from ascending infections (Gregory and Cyr, 2014; Hall et al, 2007). Among the other gene families, aldo-keto reductases are involved in the biosynthesis of signaling molecules (Volat et al, 2012), including prostaglandins (Kabututu et al, 2009), which have the potential both to mediate lumicrine signaling within the male reproductive tract as well as signaling between partners following delivery to the female reproductive tract.…”

Section: Discussionmentioning

confidence: 99%

An atlas of cell types in the mammalian epididymis and vas deferens

Rinaldi¹,

Donnard²,

Gellatly³

et al. 2020

Preprint

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Following spermatogenesis in the testis, mammalian sperm continue to mature over the course of approximately 10 days as they transit a long epithelial tube known as the epididymis. The epididymis is comprised of multiple segments/compartments that, in addition to concentrating sperm and preventing their premature activation, play key roles in remodeling the protein, lipid, and RNA composition of maturing sperm. In order to understand the complex roles for the epididymis in reproductive biology, we generated a single cell atlas of gene expression from the murine epididymis and vas deferens. We recovered all the key cell types of the epididymal epithelium, including principal cells, clear cells, and basal cells, along with associated support cells that include fibroblasts, smooth muscle, macrophages and other immune cells. Moreover, our data illuminate extensive regional specialization of principal cell populations across the length of the epididymis, with a substantial fraction of segment-specific genes localized in genomic clusters of functionally-related genes. In addition to the extensive region-specific specialization of principal cells, we find evidence for functionally-specialized subpopulations of stromal cells, and, most notably, two distinct populations of clear cells. Analysis of ligand/receptor expression reveals a network of potential cellular signaling connections, with several predicted interactions between cell types that may play roles in immune cell recruitment and other aspects of epididymal function. Our dataset extends on existing knowledge of epididymal biology, and provides a wealth of information on potential regulatory and signaling factors that bear future investigation.

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Section: Discussionmentioning

confidence: 99%

An atlas of cell types in the mammalian epididymis and vas deferens

Rinaldi¹,

Donnard²,

Gellatly³

et al. 2020

Preprint

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“…In fact, sperm autoimmunity is a considerable problem, with 5–10% of male infertility cases being attributed to sperm antibodies (Hedger, ; Lotti et al ., ), while inflammatory lesions can be found in the testes of a substantial proportion of men with idiopathic infertility (Suominen & Soderstrom, ; Schuppe et al ., ). Immunological events in the epididymis and vas deferens can have detrimental effects on spermatogenesis and fertility, and even systemic inflammation inhibits male reproduction (Gregory & Cyr, ; Fijak et al ., ). Consequently, discovering the factors that are fundamental to the regulation of the unique immunological milieu of the epididymis would shed light on many factors contributing to male infertility.…”

Section: Background and Clinical Significancementioning

confidence: 99%

Activins, follistatin and immunoregulation in the epididymis

Wijayarathna

Hedger

2019

Andrology

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Background: The interface between the epididymis and the immune system is implicated in many male reproductive pathologies. The resident immune cell populations and immune-environment within the epididymis are significantly different from the testis, which is an immune-privileged site. Moreover, the immune cell subsets and immunological responses between different regions of the epididymis vary considerably. The cauda epididymis is more susceptible to autoimmune responses than the caput in rodent models of active immunization or suppressed immune tolerance, and in men with congenital or physical damage to the reproductive tract. Activins are members of the transforming growth factor-b family of cytokines that are crucial for testis and epididymal development; however, they also have complex immunoregulatory properties and may play an essential role in the regulation of immunity in the reproductive tract. Materials and methods: Our recent research and relevant publications by other researchers identified following a PubMed search are reviewed. Results: The caput epididymis displays elevated endogenous expression of activins A and B and the immunoregulatory gene, indoleamine-2,3-dioxygenase, co-existing with an extensive population of intra-epithelial and interstitial macrophages and dendritic cells, which appear to be involved in regulating tolerance against sperm antigens. The caput is also relatively resistant to inflammatory damage caused by autoimmunity or bacterial infection, but the cauda, which exhibits low activin expression and high levels of the activin-binding protein, follistatin, is highly susceptible to inflammatory damage. Paradoxically, inflammation in the cauda induces increased activin production, and inhibition of activin activity reduces inflammatory responses. Studies using mouse models with altered levels of activins and follistatin indicate a relationship between the activins and genes involved in inflammation and immunoregulation. Conclusion: The existing data indicate that activins play a complex role in controlling inflammation and immunity in the epididymis and vas deferens.

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“…ABC transporters are a protein superfamily characterized by the presence of ATP-binding cassette (ABC) domains that are involved in inward and outward transport of a wide variety of substrates such as metabolites, drugs, and lipids. In particular, our analysis demonstrates that the ABC transporters play a key role in epididymal biochemistry of sperm membrane rearrangement [Ouvrier et al 2009;Jones and Cry 2011;Morales et al 2012;Caballero et al 2012;Gregory and Cyr 2014;Palme et al 2014]. They are a superfamily of more than 250 transmembrane proteins characterized by a region that spans about 180 amino acids and contains three highly conserved motifs: the Walker A/P-loop (12 amino acids), a signature motif/ C-loop (5 amino acids), and the Walker B motif (5 amino acids) [George and Jones 2012].…”

Section: Node Degreementioning

confidence: 65%

The maturation of murine spermatozoa membranes within the epididymis, a computational biology perspective

Bernabò

Agostino

Ordinelli

et al. 2016

Systems Biology in Reproductive Medicine

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(2016) The maturation of murine spermatozoa membranes within the epididymis, a computational biology perspective, Systems Biology in Reproductive Medicine, 62:5, 299-308, DOI: 10.1080/19396368.2016 To link to this article: https://doi.org/10. 1080/19396368.2016.1205679 To become fertile, mammalian spermatozoa require completing a complex biochemical maturation that begins in the testis and ends within the female oviduct. Here, we paid attention to the events occurring at the membrane level during the epididymal transit. Indeed, in the epididymis, the molecular composition and the physical-chemical proprieties of sperm membranes markedly change, with functional cross talking among the spermatozoa, the epithelium, and the luminal content (particularly the epididymosomes). To study this process, we undertook a biological networks study, representing the involved molecules as nodes and their interactions as links. The analysis of network topology revealed that it has a scale free and small world architecture and it is robust against random failure. That assures a fast and efficient transmission of information and it leads to identifying the molecules exerting a higher level of control on the system, among which cholesterol plays a pivotal role. The reactome enrichment analysis allowed the reconstruction of the biochemical pathways involved in sperm epididymal maturation and STRING analysis permitted the identification of molecular events possibly involved in that process. In conclusion, this approach allows inferring interesting information, thus contributing to the knowledge on this process and suggesting staring points for further research. ARTICLE HISTORY

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The blood-epididymis barrier and inflammation

Cited by 65 publications

References 163 publications

An atlas of cell types in the mammalian epididymis and vas deferens

An atlas of cell types in the mammalian epididymis and vas deferens

Activins, follistatin and immunoregulation in the epididymis

The maturation of murine spermatozoa membranes within the epididymis, a computational biology perspective

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