Background and Objectives: The male urethra is a complex structure that plays a critical role in genitourinary health and function. Despite its importance, histological descriptions of the penile urethra, particularly its epithelial components, remain incomplete. This study offers a comprehensive histological analysis of the penile urethra, focusing on the epithelium across distinct anatomical regions, including the glans, distal and proximal fossa navicularis and spongy urethra. Materials and Methods: Utilizing five human penile specimens, we employed various staining techniques to elucidate the structural characteristics of these epithelial tissues. Results: Our findings reveal notable variations in epithelial composition, such as the presence of glycogen-rich cells in the distal fossa navicularis and the presence of mucous glands in the spongy urethra and proximal fossa navicularis. Additionally, we identified a previously underreported valvule-like structure in the distal fossa navicularis in two of the specimens. In addition, the epithelium of the glans and the distal fossa navicularis are thicker than the ones of the proximal fossa navicularis and the spongy urethra. With a similar vascular density, the orientation of the blood vessels also diverges starting with the distal fossa navicularis. Conclusions: This study provides new insights into the histological organization of the penile urethra, offering critical reference data that can enhance our understanding of urethral pathologies and improve the outcomes of surgical interventions, particularly in the context of tissue engineering and reconstructive surgery.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease.¹ The primary clinical signs of PD are motor symptoms that include resting tremors, muscular rigidity, and slowness of movements.² The initial treatment of PD usually starts by administering the dopamine precursor l-dopa. However, over time, this pharmacological treatment becomes less effective, and most patients will eventually suffer from l-dopa-induced dyskinesia.^3,4 For these patients, deep brain stimulation (DBS) surgery is often the recommended treatment option.⁵

Sebaceous glands contribute to skin physiology by producing sebum, which forms a lipid barrier preventing dehydration. Various skin conditions, including acne vulgaris and seborrheic dermatitis, are linked to their dysfunction. Several questions remain concerning the formation and regulation of these glands as there are few human tridimensional models available to address them. Herein, we investigated the conditions that allow sebaceous gland formation in human tissue-engineered skin substitutes. We tested whether the source of epithelial cells, fibroblasts, and the extracellular environment influence the sebaceous gland formation in vitro and after grafting onto mice. Our results showed that sebaceous glands formed in substitutes produced with epithelial cells derived from scalp but were absent in those generated from foreskin or breast skin tissues, whereas the fibroblast origin did not affect this process. However, no sebaceous gland was found in substitutes produced from decellularized dermal matrices that were recellularized with fibroblasts and scalp epithelial cells, suggesting that some extracellular cues lost after decellularization play a major role in sebaceous gland formation. Our work establishes an unprecedented model to study human sebaceous gland formation and function and will likely be instrumental to investigate the pathogenesis of various diseases of the sebaceous gland in the future.

Objectives: The male urethra is a complex structure that plays a critical role in genitourinary health and function. Despite its importance, histological descriptions of the penile urethra, par-ticularly its epithelial components, remain incomplete. This study offers a comprehensive his-tological analysis of the penile urethra, focusing on the epithelium across distinct anatomical regions, including the glans, distal and proximal fossa navicularis, and spongy urethra. Meth-ods: Utilizing four human penile specimens, we employed various staining techniques to eluci-date the structural characteristics of these epithelial tissues. Results: Our findings reveal notable variations in epithelial composition, such as the presence of glycogen-rich cells in the distal fos-sa navicularis and the presence of mucous glands in the spongy urethra and proximal fossa na-vicularis. Additionally, we identified a previously underreported valvule-like structure in the distal fossa navicularis in two of the specimens. Conclusions: This study provides new insights into the histological organization of the penile urethra, offering critical reference data that can enhance our understanding of urethral pathologies and improve the outcomes of surgical inter-ventions, particularly in the context of tissue engineering and reconstructive surgery.

Cell identity within the human urogenital tract is strongly influenced by hormonal signaling, yet increasing evidence suggests that epithelial differentiation may also be shaped by microenvironmental cues. In this study, we investigated how hormonal and physical environments modulate epithelial identity and plasticity using a human tissue-engineered urethral model. Primary epithelial and stromal cells derived from vaginal and trans-women’s urethral tissues were combined in homologous and heterologous configurations and cultured under controlled conditions. Constructs were exposed to estradiol or dihydrotestosterone, and epithelial differentiation was assessed using histological staining and immunofluorescence targeting lineage-specific markers. Our results show that vaginal epithelial cells cultured on vaginal stroma maintain a stable vaginal phenotype characterized by epithelial stratification and glycogen accumulation, although the magnitude of these features was modulated by hormonal stimulation. In contrast, urethral epithelial cells displayed a high degree of plasticity, adopting distinct phenotypes depending on the physical-culture environment. Notably, constructs containing urethral epithelium developed a dual phenotype, with vaginal-like differentiation at the air–liquid interface and a more urethral-like organization in immersed conditions. Furthermore, urethral cells derived from long-term estrogen-exposed tissues exhibited persistent expression of both urethral and vaginal markers, suggesting incomplete or hybrid differentiation states. Overall, these findings demonstrate that epithelial identity in the human urethra is not fixed but dynamically regulated by an interplay between intrinsic cellular properties, stromal interactions, and physical microenvironmental cues, while hormonal signaling alone appears insufficient to dictate cell fate. This study provides new insights into epithelial plasticity and has important implications for both developmental biology and tissue-engineering approaches to urogenital reconstruction.