Expression of NOD1 and NOD2 transcripts in the healthy and diseased equine endometrium

Abstract

In mares, endometrial diseases are the main cause of reduced fertility and have a high financial impact on equine breeding. Of particular importance are subclinical diseases, since they can only be diagnosed by the histological examination of an endometrial biopsy. Moreover, the precise pathogenesis of some frequent subclinical diseases, i.e. nonsuppurative endometritis and endometrosis (periglandular fibrosis), is unknown. The reason for the increased susceptibility of some mares to develop a persistent postbreeding endometritis (PPBE) is also still unsolved. The nucleotide-binding oligomerization domain proteins 1 and 2 (NOD1 and NOD2) are innate immunity receptors of epithelial and antigen presenting cells. On the one hand, they defend against intracellular bacteria and thus help to prevent and clear tissue infections. On the other hand, their altered expression can contribute to tissue inflammation and fibrosis. It has been shown that NOD1 and NOD2 are also involved in the pathogenesis of uterine diseases in women and other species. To the best of the authors' knowledge, no data are published in regard to the expression of NOD1 and NOD2 in the equine endometrium. The aim of this study was to examine if NOD1 and NOD2 transcripts are expressed in the healthy and diseased equine endometrium. Endometrial samples of 31 adult mares were investigated by PCR and histology. The former was performed in comparison on native and formalin-fixed paraffin embedded (FFPE) samples. By PCR, transcripts of NOD1 and NOD2 were detected in native and FFPE endometrial samples of all 31 mares. The morphology of endometrial glands was secretory (n = 19), proliferative (n = 6) or in transition between both stages (n = 6). Five tissue samples had no pathological alterations; two of these were from a gravid mare. The remaining showed one or several endometrial diseases including different forms of endometritis (n = 12), endometrosis (n = 20), angiosclerosis (n = 20), perivasculitis and vasculitis (n = 1), infiltration with neoplastic lymphocytes (n = 1) and placental retention (n = 1). Results of this study are consistent with a constitutive expression of NOD1 and NOD2 transcripts during all stages of the endometrial cycle within the healthy and diseased equine endometrium. They imply a functional importance of NOD1 and NOD2 in the equine endometrium for the regulation of physiological processes as well as the pathogenesis of endometrial diseases. In human beings, certain polymorphisms and mutations of NOD genes have been identified as predisposing factors for chronic inflammation. Thus, it appears possible that NOD gene polymorphisms may also contribute to the resistance or susceptibility of mares to develop PPBE. This study provides the basis for future investigation into the contribution of NOD1 and NOD2 to the pathogenesis of equine endometrial diseases. The results of those future studies may reveal information that is beneficial for the prevention and treatment of equine endometrial diseases.