Regulatory roles of IFN-gamma in human endometrium

Available data suggest that several microenvironments exist within the complex structure of human endometrium. Predecidual reaction which is associated with the expression of VLA-1 and alpha 1 PEG first appears in the stromal cells around the spiral arteries. Expression of Ber-EP4 is limited to a distinct group of stromal cells that reside around glands and underneath surface epithelium. A distinctly different group of stromal cells that surround lymphoid cells express HLA-DR molecules. The proliferative activity of endometrial epithelium is markedly higher in the upper functionalis and is gradually diminished towards the basalis. In addition, several proteins, including HLA-DR and some members of the integrin family of molecules are strongly expressed in the basalis epithelium. The expression of these proteins in endometrial epithelium is gradually diminished towards the surface. The gradual rather than abrupt changes in the expression of proteins and proliferative activity across the length of endometrial epithelium argues against separation of endometrium into the distinct regions of basalis and functionalis. Rather, such distribution is in favor of existence of a polarized microenvironment in human endometrium. Emerging evidence suggests that the development of this microenvironment is mediated by T cells activated within lymphoid aggregates with consequent secretion of IFN-gamma. IFN-gamma regulates HLA-DR expression and proliferation of endometrial epithelium. Maximal impact of the cytokine is exerted in regions close to the source of cytokine with a gradual dissipation of the effect distant from this source. Therefore, this cytokine may be the prototype of a group of paracrine factors that induce a polarized microenvironment in human endometrium.