Neuroendocrine Cells of the Prostate Derive from the Neural Crest

The histogenesis of prostatic neuroendocrine cells is controversial: a stem cell hypothesis with a urogenital sinus-derived progeny of all prostatic epithelial cells is opposed by a dual origin hypothesis, favoring the derivation of neuroendocrine cells from the neural crest, with the secretory and basal cells being of urogenital sinus origin. A computer-assisted 3D reconstruction was used to analyze the distribution of chromogranin A immunoreactive cells in serial sections of human fetal prostate specimens (gestation weeks 18 and 25). Immunohistochemical double labeling studies with YFP and serotonin antisera combined with electron microscopy were carried out on double-transgenic Wnt1-Cre/ROSA26-YFP mice showing stable YFP expression in all neural crest-derived cell populations despite loss of Wnt1 expression. 3D reconstruction of the distribution pattern of neuroendocrine cells in the human fetal prostate indicates a migration of paraganglionic cells passing the stroma and reaching the prostate ducts. Double-transgenic mice showed 55% double labeling of periurethral neuroendocrine cells expressing both serotonin and YFP, whereas single serotonin labeling was observed in 36% and exclusive YFP labeling in 9%. The results favor the assumption of a major fraction of neural crest-derived neuroendocrine cells in both the human and murine prostates.