# Quiet residents of the vaginal epithelium: immunohistochemical study on the distribution and role of human vaginal Merkel cells

## TL;DR

This study explores the role of Merkel cells in the human vaginal epithelium and finds they likely do not function as mechanoreceptors but may support tissue homeostasis.

## Contribution

First study to investigate the function of Merkel cells in the vaginal epithelium and their potential endocrine role.

## Key findings

- Merkel cells in the vaginal epithelium lack PIEZO2 and CGRP, suggesting they are not mechanoreceptors.
- Merkel cells show a distinct immunophenotype, indicating a possible endocrine function.
- Merkel cells are non-innervated and localized in the basal epithelial layers.

## Abstract

Although Merkel cells (MCs) are well-established mechanoreceptors in human skin, their function within the vaginal epithelium remains undefined. The aim of the present histological study was to investigate whether MCs located in the stratified epithelium of the anterior wall of the human vagina exhibit similar mechanosensory functions to those observed in the skin.

Immunohistochemical analysis was performed on vaginal wall samples from eight women undergoing transabdominal or laparoscopic surgery. Immunohistochemical markers including cytokeratin 20 (CK20), neuron-specific enolase (NSE), synaptophysin (SYN), chromogranin A (CHRA), vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), PIEZO2 and protein gene product 9.5 (PGP9.5) were used to identify MCs and assess their distribution and phenotype. To better demonstrate the connection of MCs with nerve fibres, we used sequential double immune-enzymatic technique with different markers for MCs and for nerve fibres (primary antibodies against CK20 and PGP 9.5) and confirmed that none of examined MCs was in contact with the nerve fibre.

MCs were identified as CK20-positive in all specimens (100%), NSE-positive in 88%, SYN-positive in 25%, CHRA-positive in 100%, and VIP-positive in 25%. No samples demonstrated positivity for CGRP and PIEZO2. MCs were localized predominantly in the basal epithelial layers as solitary cells, with CK20 the most effective detection method. Sequential double immune-enzymatic technique confirmed non- innervated Merkel cells with dendritic morphology.

This is the first study to address the possible function of MCs in the vaginal epithelium. The absence of PIEZO2 and CGRP expression, and low expression of VIP and SYN, suggests a non-mechanosensory and non-nociceptive role for MCs in the vaginal epithelium. The immunophenotypic profile supports a potential endocrine (paracrine or autocrine) function distinct from their role in human skin. Vaginal MCs probably form part of the neuroendocrine system of the vagina and maintain vaginal epithelial homeostasis and regeneration.