RT Journal Article T1 The sensory penis: A comprehensive immunohistological and ontogenetic exploration of human penile innervation A1 Cepeda Emiliani, Alfonso A1 Otero Alén, María A1 Suárez Quintanilla, Juan A1 Gándara Cortés, Marina A1 García-Caballero Parada, Tomás A1 Gallego Gómez, Rosalía A1 García-Caballero, Lucía K1 Foreskin K1 Immunohistochemistry K1 Mechanoreceptors K1 Nerve endings K1 Penis K1 Peripheral nervoussystem AB 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. PB Wiley SN 2047-2919 YR 2025 FD 2025-09-19 LK https://hdl.handle.net/10347/43636 UL https://hdl.handle.net/10347/43636 LA eng NO 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 NO 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. DS Minerva RD 28 abr 2026