On the chemosensory nature of the vomeronasal epithelium in adult humans

Abstract

In contrast to many lower vertebrates, the vomeronasal epithelium (VNE) in humans has long been regarded as absent or functionally irrelevant. For example, the neural connection between the VNE and the accessory olfactory bulb has been reported to degenerate during the second half of pregnancy and its presence has not been demonstrated in adults. Further, reports on the organ's occurrence in adult humans have been contradictory. The aims of this study were to collect immunohistochemical data on the neurogenic or epithelial character of the VNE [for example, with antibodies against protein gene product 9.5 (PGP 9.5), olfactory marker protein (OMP), beta-tubulin, and cytokeratin], determine its proliferative capacity (for example, proliferating cell nuclear antigen), as well as to examine the differentiation activity of VNE cells and their interactions with extracellular matrix components (for example, hyaluronan receptor CD44, galectins, and caveolin). To this end, we studied the vomeronasal organs (VNOs) of 22 human cadavers, three adult biopsies, one embryo (week 8) and one fetus (week 13) by means of immunohistochemistry. The histology of the VNE appeared extremely heterogeneous. There were sections of stratified, respiratory, and typical "pseudostratified" vomeronasal epithelia consisting of slender bipolar cells. Mostly negative immunohistochemical results for OMP indicated that the human VNE does not function like the mature olfactory epithelium. In addition, the investigations did not support the hypothesis that neural connections between the VNE and central brain structures might be present. On the other hand, the presence of some bipolar cells positive for both PGP 9.5 and soybean lectin (SBA) pointed to a neuron-like activity of a small subset of VNE cells. Proliferation antigens located in the nuclei of basally located cells of the VNE were not regularly expressed. However, positive reactions for CD44 demonstrated a high activity of VNE cells in terms of differentiation and migration. Some bipolar cells showed immunoreactivity for caveolin indicating its possible role in signal transduction and differentiation. In summary, the reaction patterns of most antibodies in the adult human VNE are different from those obtained in the olfactory epithelium and the VNO of the rat. However, the VNE shows a specific pattern of activity unique to the mucosa of the nasal cavity. Considering the histologically well differentiated epithelium and its steady maintenance, the VNE of the adult human appears to be a highly differentiated structure the function of which remains unclear.

Comparative study of lectin reactivity in the vomeronasal organ of human and nonhuman primates

“…Although the precise significance of the lectin patterns described herein for primates is not known at this time, our findings support other recent studies contending that the human VNO is nonchemosensory in nature (Trotier et al, 2000;Bhatnagar and Smith, 2001;Smith et al, 2002;Witt et al, 2002).…”

“…A notable characteristic of the human VNO was PNA reactivity in some intermediate-level cells. These cells could be neuronal since small numbers of cells react with neuronal markers, including olfactory marker protein, in the human VNO (Takami et al, 1993;Witt et al, 2002). Yet no clear link to VRNs is possible at this time.…”

“…Yet, based on a series of physiological studies, one group of authors has concluded that the human VNO is functional, i.e., with at least some functional similarity to the VNO of other mammals (Berliner et al, 1996;Monti-Bloch et al, 1998;Grosser et al, 2000). The aforementioned anatomical and physiological findings have been difficult to reconcile, and immunohistochemical studies have added some degree of ambiguity by revealing small populations of cells expressing various neuronal markers in the human VNO (Takami et al, 1993;Witt et al, 2002). Therefore, the present study was undertaken to add observations of lectin reactivity in the human and chimpanzee VNO to describe further the morphology relative to other primates, particularly lemurs and lorises, which are known to possess VNOs that assess chemical cues conveying reproductive information (Schilling et al, 1990;Aujard, 1997).…”

Human vomeronasal epithelium development: An immunohistochemical overview

“…Cytokeratins are considered supplemental markers to aid in differentiation of non-sensory cells from sensory cells in the olfactory epithelium [23,24] and the VN epithelium [5]. While horizontal basal cells of the olfactory epithelium usually show intense immunoexpression for cytokeratin [24,25] our results regarding the VN epithelium do not show a basal layer comparable to the one found in the olfactory epithelium, neither lacunae of negative reactions that might indicate the presence of chemosensory cells [26]. Pan-Ctk results of the present study demonstrate that during the studied foetal age intervals almost all VN epithelial cells display structural components associated to cytokeratins, suggesting the gradual transformation of putative neural precursors into epithelial cells.…”

Facts, fallacies, fears, and frustrations with human pheromones

“…Hence, at the genomic and Fischer Hansen (1996a, 1996b). e Trotier et al (2000); Witt et al (2002). f One V1R1L gene is expressed in the olfactory epithelium (Rodriguez et al, 2000); others may be intact, but expression has not been identified in the VNO .…”