Positional relationship between natural killer cells and distribution of sympathetic nerves in decidualized mouse uterus.

Abstract

Uterine natural killer (uNK) cells are the most abundant leukocytes in pre-implantation endometrium and early pregnancy deciduas in humans and rodents. They are associated with structural changes in maternal spiral arteries but regulation of their recruitment and activation is incompletely understood. The major subpopulation of uNK cells in humans expresses CD56, the neural cell adhesion molecule (NCAM)-1 while their counterpart in mouse expresses asialoGM1, a brain ganglioside. Sympathetic nerves express NCAM-1 which mediates homotypic binding. Sympathetic fibers innervate the mesometrial vasculature but their relationship to the myometrial and decidual uNK cell recruitment is unknown. The present study aims to explore positional relationship between natural killer cells and distribution of nerves in decidualized mouse uterus. Immunohistochemistry and mRNA expression for the enzyme tyrosine hydroxylase were used to map sympathetic nerve fibre distribution within C57BL/6 implantation sites and to address a relationship with uNK cells. Tyrosine hydroxylase positive neurons were identified in the mesometrium closely associated with uterine arteries. Staining became gradually vanished as the nerves crossed the myometrium and entered the decidualized uterus. No neuronal stain was associated with the spiral arteries. Periodic Acid Schiff's reactive uNK cells were absent from the mesentery, but abundant in decidua basalis where they are associated with non-innervated vessels. Data suggest that the recruitment of uNK progenitor cells to the uterus is unlikely to be dependent on signaling by the sympathetic nervous system.