The sensory penis: A comprehensive immunohistological and ontogenetic exploration of human penile innervation

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Abstract

Background: Penile sexual sensation relies on intricate neural structures that remainincompletely characterized. Immunohistological insights into their development andorganization can enhance understanding of penile neuroanatomy and function, whileoptimizing surgical outcomes. Objectives: To elucidate the ontogeny, organization, and immunohistological featuresof human penile innervation in fetal and adult specimens, primarily focusing on thefrenular delta, sensory corpuscles, and related structures to address gaps in anatomicalknowledge and inform surgical practices. Materials and methods: Formalin-fixed, paraffin-embedded tissues from 30 fetal (8–24 weeks) and 14 adult cadaveric penile specimens were analyzed. Routine histologicalstains and immunohistochemical markers targeting neural structures were applied.Serial sections were examined for histology, neuroanatomical mapping, sensorycorpuscle characterization, and neural density assessments. Results: Fetal penile neurodevelopment exhibited two phases: the pre-corpuscularstage (8–16 weeks), marked by axonal hyperinnervation and exuberant ventral intraep-ithelial nerve fibers, and the corpuscular stage (17–24 weeks), characterized byPacinian corpuscle emergence and targeted neural pruning. Adult specimens showedregion-specific neural distributions, with heightened densities in the frenular delta.Intracorporeally, sensory corpuscles exhibited a bimodal intraspongiosal distribution,with Pacinians in the bulb and glans. Molecular profiles of sensory corpuscles, includingnovel immunoreactivities, were comprehensively documented. The preputial dartosand vasculature displayed dense autonomic innervation. A superficial glans tunicaalbuginea was identified, with implications for neural organization. Discussion: These findings reveal previously unrecognized transitions during fetalpenile neural development and into adulthood, providing a foundation for the neurode-velopmental biology of the human penis and documenting the frenular delta’s uniqueinnervation. The characterization of penile neural components and the glans tunica albuginea addresses longstanding anatomical and sexological questions. Our resultsinform current debates on penile circumcision and neurotomy. Conclusion: This study provides a comprehensive ontogenetic framework of penileinnervation, emphasizing the frenular delta as a specialized center of sexual sensation.

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Cepeda-Emiliani, A., Otero-Alén, M., Suárez-Quintanilla, J., Gándara-Cortés, M., García-Caballero, T., Gallego, R., & García-Caballero, L. (2025). The sensory penis: A comprehensive immunohistological and ontogenetic exploration of human penile innervation. Andrology, n/a10.1111/andr.70118

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We express our deepest gratitude to those who donated their bodies to science, and to their families, for enabling anatomical researchthat advances scientific knowledge and improves patient care. We aregrateful to Professor María Teresa Vázquez Osorio for providing accessto specimens from the Body Donation and Dissecting Room Centerof the Complutense University of Madrid. We also thank AlejandroGarcía-Pérez for contributing the artwork in Figures 1A,B and 6A–D, as well as the anonymous reviewers for their valuable feedback.

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© 2025 The Author(s). Andrology published by John Wiley & Sons Ltd on behalf of American Society of Andrology and European Academy of Andrology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in anymedium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.© 2025 The Author(s). Andrology published by John Wiley & Sons Ltd on behalf of American Society of Andrology and European Academy of Andrology.
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