Physiopathologic mechanisms involved in mare endometrosis.

This study investigates the mechanisms leading to endometrosis, a common cause of infertility in mares. It reveals that neutrophils, types of white blood cells, respond to infections by releasing neutrophil extracellular traps (NETs) which not only fight off microbes but may also contribute to the endometrial fibrosis characteristic of endometrosis. The study further explores the role of specific enzymes and cytokines in this process.

Mechanisms of Endometrosis in Mares

This research focuses on understanding the chronic inflammatory process that results in endometrosis in mares. Endometrosis is a condition characterized by excessive fibrous connective tissue proliferation in the endometrium (the inner lining of the uterus) leading to fertility issues.

• The study brings attention to the systemic neutrophils, which are a part of the immune system, arriving at the uterus in response to mating or presence of pathogens.
• These neutrophils react to infectious stimuli by spewing out their DNA to form NETs, which are structures that immobilise and eliminate pathogens.
• However, a key revelation of this study is the possibility of these NETs contributing to endometrial fibrosis, the defining feature of endometrosis, due to their long-term exposure to the endometrium.

The Role of NET components and Cytokines

Diving further into the molecular mechanisms, the study identified various key enzymes and cytokines involved with the formation of these NETs and subsequently, the process of fibrosis:

• The components of NETs such as myeloperoxidase, elastase, and cathepsin G, when exposed to the endometrium for a prolonged period, up-regulated fibrosis markers like TGFβ and TIMP-1.
• It was also observed that pro-fibrotic cytokines regulated the deposition of collagen, a key player in fibrosis.
• Changes in expression of other factors like connective tissue growth factor (CTGF) and specific interleukins (IL) were also noted in endometrium with varying degrees of fibrosis and/or inflammation.
• The research thus suggests a potential role for CTGF, IL and NETs components in the development of endometrosis in mares.

Prostaglandins and Endometrial Fibrosis

An additional proposition made by the researchers is that prostaglandins, compounds with hormone-like effects, could also be implicated in endometrial fibrosis:

• In a condition of sustained endometritis (inflammation of the endometrium), prostaglandins not only cause early luteolysis (degradation of the corpus luteum) or early pregnancy loss, but may also augment the pathogenesis of fibrosis by stimulating collagen deposition.