What Goes Wrong from a Mare Healthy Endometrium to Endometrosis

Mare endometrial function involves innumerous mediators as hormones (progesterone, estradiol, oxytocin, prostaglandins), cytokines, nitric oxide, enzymes and others. When this complex interaction is disrupted reproductive function is impaired. While some mares carry on a pregnancy to term, others develop recurrent post-breeding endometritis and chronic degenerative fibrosis (endometrosis), leading to infertility. Endometrosis is also linked to oviduct fibrosis, which exacerbates infertility. A thorough etiology, diagnosis and pathogenesis of equine endometrosis is still incomplete. In the uterus, equine neutrophils may release neutrophil extracellular traps (NETs). Besides holding bacteria in loco and kill them, they have a deleterious effect by inducing collagen formation. Our in vitro studies have shown that NETs persistence might be linked to endometrosis, due to NETs proteases action, mainly elastase and cathepsin G. These NETs proteases increase PGF2α synthesis or PGF2α receptor transcripts. Also impaired PGE2 or PGE2 receptor 2 transcripts are associated to higher collagen type I production, characteristic of fibrosis. In order to fight NETs fibrotic effect, the use of an elastase inhibitor stimulated the in vitro production of anti-fibrotic PGE2 and inhibited the pro-fibrotic PGF2α. Since these are promising results, further studies should be performed to reduce the establishment of mare endometrial fibrosis in susceptible mares.