Background The epididymis is the hallmark of all vertebrate species practicing internal fertilization. While the functions of the epididymis are well documented in laboratory rodents and some domestic animals, the structure and functions of the epididymis in humans remain poorly documented. Objectives Using human tissues obtained with the collaboration of our local organ transplantation program, the histology, cell types, and three-dimensional organization of the excurrent duct were investigated. Microarrays were performed to determine the gene expression pattern along the human epididymis. Materials and methods The histology of longitudinal sections of the proximal epididymis was described, and immunohistochemistry using specific antibodies was used to characterize cell types of the efferent duct and caput epididymis epithelia. The epididymis was divided into eight segments permitting gene profiling by microarray and gene ontology analysis. Results The proximal region of the human epididymis is formed exclusively by efferent ducts. These ducts form a complex histological structure particularly at the junction of the efferent ducts and caput epididymis. The efferent ducts exhibit a specific cellular signature when compared with the adjacent epididymis tubule. Efferent duct gene expression is not segmented and is dedicated to cilium differentiation and movement. The gene expression pattern of the caput segment is homogeneous and specialized in defense and immune responses and fertilization. Discussion In murine species, the epididymis is segmented into the initial segment, caput, corpus, and cauda regions, whereas in humans, the proximal region is formed by efferent ducts. The caput tubules have their own histological organization with a well-defined gene expression pattern. The distal corpus and cauda epididymis are distinct by a limited number of differentially expressed genes. Conclusions Knowledge of epididymis functions and structure obtained using laboratory species should be extrapolated to humans with caution.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/andr.12633

Revisiting structure/functions of the human epididymis

Embryonic development of the mouse salivary glands begins with epithelial thickening and continues with sequential changes from the pre-bud to terminal bud stages. After birth, morphogenesis proceeds, and the glands develop into a highly branched epithelial structure that terminates with saliva-producing acinar cells at the adult stage. Acinar cells derived from the epithelium are differentiated into serous, mucous, and seromucous types. During differentiation, cytokeratins, intermediate filaments found in most epithelial cells, play vital roles. Although the localization patterns and developmental roles of cytokeratins in different epithelial organs, including the mammary glands, circumvallate papilla, and sweat glands, have been well studied, their stage-specific localization and morphogenetic roles during salivary gland development have yet to be elucidated. Therefore, the aim of this study was to determine the stage and acinar cell type-specific localization pattern of cytokeratins 4, 5, 7, 8, 13, 14, 18, and 19 in the major salivary glands (submandibular, sublingual, and parotid glands) of the mouse at the E15.5, PN0, PN10, and adult stages. In addition, cell physiology, including cell proliferation, was examined during development via immunostaining for Ki67 to understand the cellular mechanisms that govern acinar cell differentiation during salivary gland morphogenesis. The distinct localization patterns of cytokeratins in conjunction with cell physiology will reveal the roles of epithelial cells in salivary gland formation during the differentiation of serous, mucous or seromucous salivary glands.

Immunolocalization patterns of cytokeratins during salivary acinar cell development in mice.

Activin over-expression in the testis of mice lacking the inhibin α-subunit gene is associated with androgen deficiency and regression of the male reproductive tract.

In a 26-week carcinogenicity study in rasH2-Tg mice, squamous cell carcinoma on the epididymis was observed in a male mouse in the positive control group treated with N-methyl-N-nitrosourea. A 29-week-old male rasH2-Tg mouse that was euthanized 21 weeks after the administration of N-methyl-N-nitrosourea had a white-grayish mass on the left caput epididymis. The mass was nodular and consisted of pleomorphic tumor cells forming alveolar, sheeted, and trabecular structures suggesting epithelial tumor growth. These cells presented a cobblestone-like arrangement and formed intercellular bridges. Keratinization was infrequently observed. Periodic acid-methenamine-silver staining revealed argyrophilic fibrous structures around the alveolar structure of the tumor cells. Immunohistochemically, the tumor cells were positive for cytokeratin AE1/AE3 and cytokeratin 14 and negative for cytokeratin 5, p63, uroplakin III, vimentin, desmin, and αSMA. These immunohistochemical results suggested the tumor cells originated from the epididymal ducts. Metastatic lesions were observed in the mesenteric, inguinal, and pancreaticoduodenal lymph nodes. Based on these results, this tumor was diagnosed to be a primary squamous cell carcinoma of the epididymis. This is the first report of primary squamous cell carcinoma of the epididymis in a rasH2-Tg mouse.

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Primary epididymis squamous cell carcinoma in a CB6F1-Tg rasH2 mouse

The epididymis is a male genital organ that has plays various functions, including sperm concentration, maturation, and storage. The epididymal epithelium consists of principal cells, clear cells, and basal cells. To comprehensively understand the occurrence and morphological differentiation of basal cells, we examined the expression and localization of cytokeratins (CKs) in the epididymal epithelium during postnatal development of the mouse. Immunohistochemical staining showed that, in adult mice, CK5 and CK14 were exclusively expressed in the cytoplasm of basal cells. During postnatal development, basal cells that stained positive for CK5 and CK14 first appeared in immature columnar epithelial cells in mice aged 1 week. The immunoreactivity became progressively stronger in mice aged 2-3 weeks. In mice aged 3 weeks, the immunoreactivity was strong in regions IV and V. In mice aged ≥ 4 weeks, strong immunoreactivity was observed in all epididymal regions. CK5 and CK14 could be useful markers of differentiation in epididymal basal cells. These basal cells originate from immature columnar epithelial cells and are of two types—dome-shaped and flask-shaped—. The flask-shaped cells are mainly located in the initial segment of the mouse epididymis.

Kana Murakami

Papers

Cytokeratin localization and basal cell differentiation in the epididymal epithelium during postnatal development of the mouse