Objectives: To determine the histogenetic origin of prostate neuroendocrine cells in human embryos.
Methods: Prostatic tissue in human fetuses, ranging in gestational age from early week 10 to term, and infantile and pubertal glands were studied immunohistochemically. The distribution of neuroendocrine cells within the developing gland was semiquantitatively determined. Antibodies against the neuroendocrine markers chromogranin A (CgA) and protein gene product 9.5 (PGP), along with markers of prostatic secretion (prostate-specific antigen [PSA], prostatic acid phosphatase [PAP]), were used. They were applied either individually or in double-labeling experiments, as well as in experiments combining CgA immunohistochemical analysis with in situ hybridization or in situ end-labeling.
Results: In embryos of less than 65-mm crown-rump length (CRL) (ie, younger than 12 weeks of gestation), the epithelium of the urogenital sinus was free of endocrine cells. On either side of the future prostatic mesenchyme, paraganglia containing CgA-immunoreactive cells are present, which start to penetrate the urogenital mesenchyme. In the late 10th week, these CgA-immunoreactive cells are found dispersed in the urogenital mesenchyme. In embryos of 65-mm CRL, when prostatic anlagen start to sprout from the urogenital epithelium, very few (but typically shaped) neuroendocrine cells appear in the urogenital sinus epithelium. Later, after the 12th week, when solid prostatic ducts have started forming, CgA-immunoreactive neuroendocrine cells are also present in these buds. The number of neuroendocrine cells in the urethral epithelium is considerably increased, and with the continuous sprouting and lumen formation of prostatic anlagen, neuroendocrine cells are transported into the future gland. Neuroendocrine cells observed in stroma of prenatal and postnatal prostates may also contribute to the neuroendocrine cell population of the gland.
Conclusions: Our results provide the first evidence that human prostate neuroendocrine cells represent a cell lineage of their own, being of neurogenic origin and therefore distinct from the urogenital sinus-derived prostate secretory and basal cells.