Cervico-vaginal mucus (CVM) - an accessible source of immunologically informative biomolecules

Abstract

Cervico-vaginal mucus (CVM), the product of epithelial cells lining the uterus, cervix and vagina, is secreted to facilitate uterine lubrication and microbial clearance. Predominantly composed of water and mucins, CVM also contains high levels of immuno-active proteins such as immunoglobulin A (IgA), lactoferrin and lysozyme which protect against infection by blocking adhesion and mediating microbial killing. The repertoire of cytokines, chemokines and antimicrobial peptides is predominantly generated by the secretions of endometrial epithelial cells into the uterine lumen and concentrated in the CVM. The quantity and relative proportions of these inflammatory biomarkers are affected by diverse factors including the estrus cycle and health status of the animal and therefore potentially provide important diagnostic and prognostic indicators. We propose that measuring molecular signatures in bovine CVM could be a useful approach to identifying and monitoring genital tract pathologies in beef and dairy cows.

Keywords: Biomarkers; Cervico-vaginal mucus; Diagnosis; Inflammation.

Fig. 1

Early postpartum, the cervix is open allowing the mixing of uterine, cervical and vaginal secretions which form the cervico-vaginal mucus (CVM). a Healthy endometrium is protected by a thin layer of mucus composed of low number of immune cells mainly polymorphonuclear cells (PMNs) and lymphocytes, commensal microbes, DNA from degraded cells, cytokines such as interleukin 1 (IL-1) and IL-6, chemokines such as IL-8, acute phase proteins (APP) such as serum amyloid A (SAA) and haptoglobin (HP) and antimicrobial peptides (AMP) such as lactoferrin and complement proteins (Chapwanya et al. ; Dadarwal et al. ; Healy et al. 2015). These immune molecules and cells prevent microbial invasion of the uterus. b After calving, the endometrium is exposed to bacterial contamination and a deep regeneration of tissue and glands as healthy inflammation. The immune system responds by recruiting more immune cells (PMNs) to the uterus and epithelial and stromal cells increase the secretion of cytokines, chemokines and APP (SAA) to fight microbes and modulate the immune response. Furthermore, mucus secretion is increased to facilitate clearance of bacteria and their toxins (Williams et al. 2005). c If early inflammation is not resolved, sustained or elevated secretion of immune proteins leads to tissue damage, delayed involution and reproductive problems (Chapwanya et al. ; Kasimanickam et al. ; Sheldon et al. 2009b). All these mediators of inflammation and immune cells are concentrated in CVM which can be profiled for biomarkers of uterine disease (Adnane et al. ; Carneiro et al. ; Healy et al. 2014)