Altered secretion of selected arachidonic acid metabolites during subclinical endometritis relative to estrous cycle stage and grade of fibrosis in mares

Mares that fail to become pregnant after repeated breeding, without showing typical signs of clinical endometritis, should be suspected of subclinical endometritis (SE). Contact with infectious agents results in altered synthesis and secretion of inflammatory mediators, including cytokines and arachidonic acid metabolites, and disturbs endometrial functional balance. To address the hypothesis that SE affects the immune endocrine status of the equine endometrium, spontaneous secretion of prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α), 6-keto-PGF1α (a metabolite of prostacyclin I2), leukotriene B4 (LTB4), and leukotriene C4 (LTC4) was examined. In addition, secretion of these factors was examined relative to the grade of inflammation, fibrosis, and estrous cycle stage. Eighty-two warmblood mares, of known breeding history, were enrolled in this study. On the basis of histopathologic assessment, mares were classified as suffering from first-grade SE, second-grade SE, or being healthy. The grade of fibrosis and the infiltration of endometrial tissue with polymorphonuclear leukocytes were examined by routine hematoxylin-eosin staining. In mares suffering from SE, the secretion profiles of PGE2, 6-keto-PGF1α, LTB4, and LTC4 were changed compared to mares that did not suffer from endometritis. The secretion of PGE2 and 6-keto-PGF1α was increased, whereas that of LTB4 and LTC4 was decreased. Secretion of 6-keto-PGF1α was increased in first- and second-grade SE (P < 0.01). The concentration of PGI2 metabolite was increased only in inflamed endometrium, independently of the inflammation grade, but was not affected by fibrosis. Prostaglandin E2 secretion was increased in second-grade SE (P < 0.05). The secretion of LTB4 decreased in both first- and second-grade SE (P < 0.05), whereas secretion of LTC4 was decreased only in second-grade SE (P < 0.05). Fibrosis did not change the secretion profile of PGE2, PGF2α, and 6-keto-PGF1α during the course of SE. However, the secretion profile of LTB4 was affected during the course of fibrosis. Evident divergences between PGE2 and PGF2α profiles and in PGE2:PGF2α ratios in the control versus SE mares observed during the course of diestrus contribute to shortened or prolonged interestrous intervals observed clinically in SE mares.