Cancer of the Epididymis

Okazaki, Ian J.; Pryor, Jon L.

doi:10.1007/978-1-4615-0679-9_33

Cited by 3 publications

(1 citation statement)

References 38 publications

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“…In the epididymis, prevention of autoimmune responses against auto-antigenic spermatozoa (which appear during puberty after the immune definition of 'self' has been established), while providing protection against ascending and blood pathogens, is a key determinant of male fertility (Da Silva and Smith, 2015). In addition, the epididymis is an immune privileged organ that rarely develops carcinomas (Okasaki and Pryor, 2002). The ability of epididymal epithelial cells to provide immunological tolerance while ensuring rapid recognition of pathogens and defense against cancer cells still remains largely uncharacterized.…”

Section: Introductionmentioning

confidence: 99%

Novel role of proton-secreting epithelial cells in sperm maturation and mucosal immunity

Battistone

Spallanzani

Mendelsohn

et al. 2019

Journal of Cell Science

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Epithelial cells are immune sensors and mediators that constitute the first line of defense against infections. Using the epididymis, a model for studying tubular organs, we uncovered a novel and unexpected role for professional proton-secreting 'clear cells' in sperm maturation and immune defense. The epididymal epithelium participates in the maturation of spermatozoa via the establishment of an acidic milieu and transfer of proteins to sperm cells, a poorly characterized process. We show that proton-secreting clear cells express mRNA transcripts and proteins that are acquired by maturing sperm, and that they establish close interactions with luminal spermatozoa via newly described 'nanotubes'. Mechanistic studies show that injection of bacterial antigens in vivo induces chemokine expression in clear cells, followed by macrophage recruitment into the organ. Injection of an inflammatory intermediate mediator (IFN-γ) increased Cxcl10 expression in clear cells, revealing their participation as sensors and mediators of inflammation. The functional diversity adopted by clear cells might represent a generalized phenomenon by which similar epithelial cells decode signals, communicate with neighbors and mediate mucosal immunity, depending on their precise location within an organ.This article has an associated First Person interview with the first author of the paper.

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Section: Introductionmentioning

confidence: 99%

Novel role of proton-secreting epithelial cells in sperm maturation and mucosal immunity

Battistone

Spallanzani

Mendelsohn

et al. 2019

Journal of Cell Science

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PTEN signaling through RAF1 proto-oncogene serine/threonine kinase (RAF1)/ERK in the epididymis is essential for male fertility

Washington

Hinton

2014

Proc. Natl. Acad. Sci. U.S.A.

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Without a fully developed initial segment, the most proximal region of the epididymis, male infertility results. Therefore, it is important to understand the development and regulation of this crucial region. In addition to distinctively high activity levels of the components of the ERK pathway, which are essential for initialsegment differentiation, the initial segment exhibits high protein and activity levels of phosphatase and tensin homolog (PTEN). To understand the role of PTEN in the regulation of the initial segment, we generated a mouse model with a conditional deletion of Pten from the epithelial cells of the proximal epididymis from postnatal day 17 (P17) onward. Shortly after Pten deletion, hypertrophy of the proximal epididymis became evident. Loss of Pten resulted in activation of the AKT (protein kinase B) pathway components from P28 onward, which in turn gradually suppressed RAF1 proto-oncogene serine/threonine kinase (RAF1)/ERK signaling through the interaction between AKT and RAF1. Consistent with progressive changes in RAF1/ERK signaling, loss of Pten progressively altered cell shape, size, organization, proliferation, and survival in the initial-segment epithelium and resulted in dedifferentiation and extensive epithelial folding. Most importantly, knockout males progressively lost fertility and became infertile from 6 to 12 mo. Spermatozoa from older knockout mice showed a lower percentage of motility and a higher percentage of flagellar angulation compared with controls, suggesting compromised sperm maturation. Therefore, under normal physiological conditions, PTEN suppresses AKT activity to maintain activation of the RAF1/ERK signaling pathway, which in turn maintains normal function of the initial segment and therefore, normal sperm maturation.S permatozoa enter the epididymis from the testes as immotile cells that are incapable of fertilization. During epididymal transit, a complex process called sperm maturation allows for conversion of spermatozoa into motile and fertilization-competent cells. The long, convoluted epididymal duct-which is ∼6 m long in humans and 1 m in mice (1)-provides a luminal fluid microenvironment that is necessary for sperm maturation (2).It is apparent that the most proximal region of the epididymis, the initial segment, plays an important role in sperm maturation. C-ros oncogene 1 (Ros1) knockout male mice that lacked prepubertal differentiation of the epididymal initial segment were healthy but infertile (3). Spermatozoa from Ros1 knockouts showed flagellar angulation, a defect in sperm maturation (4). Therefore, it is important to examine the mechanisms by which the initial segment develops, functions normally, and contributes to normal sperm maturation.The initial segment exhibits high activity levels of the ERK pathway components. The ERK pathway [also known as the RAF (RAF proto-oncogene serine/threonine kinases)/MEK/ERK pathway] is an intracellular protein kinase cascade containing at least MAPK3 and/or MAPK1 (commonly known as ERK1 and ERK2), a MAPKK (com...

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Androgenic regulation of novel genes in the epididymis

Robaire¹,

Seenundun²,

Hamzeh³

et al. 2007

Asian J Andrology

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The epididymis is critically dependent on the presence of the testis. Although several hormones, such as retinoids and progestins, and factors secreted directly into the epididymal lumen, such as androgen binding protein and fibroblast growth factor, might play regulatory roles in epididymal function, testosterone (T) and its metabolites, dihydrotestosterone (DHT) and estradiol (E2), are accepted as the primary regulators of epididymal structure and functions, with the former playing the greater role. To ascertain the molecular action of androgens on the epididymis, three complementary approaches were pursued to monitor changes in gene expression in response to different hormonal milieux. The first was to establish changes in gene expression along the epididymis as androgenic support is withdrawn. The second was to determine the sequence of responses that occur in an androgen deprived tissue upon re-administration of the two metabolites of T, DHT and E2. The third was to study the effects of androgen withdrawal and re-administration on gene expression in immortalized murine caput epididymidal principal cells. Specific responses were observed under each of these conditions, with an expected major difference in the panoply of genes expressed upon hormone withdrawal and re-administration; however, some key common features were the common roles of genes in insulin like growth factor/epidermal growth factor and the relatively minor and specific effects of E2 as compared to DHT. Together, these results provide novel insights into the mechanisms of androgen regulation in epididymal principal cells.

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Cancer of the Epididymis

Cited by 3 publications

References 38 publications

Novel role of proton-secreting epithelial cells in sperm maturation and mucosal immunity

Novel role of proton-secreting epithelial cells in sperm maturation and mucosal immunity

PTEN signaling through RAF1 proto-oncogene serine/threonine kinase (RAF1)/ERK in the epididymis is essential for male fertility

Androgenic regulation of novel genes in the epididymis

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