Vaginal neutrophils eliminate sperm by trogocytosis

Abstract

STUDY QUESTION What is the vaginal polymorphonuclear (PMN) spermicidal mechanism to reduce the excess of sperm? SUMMARY ANSWER We show that PMNs are very efficient at killing sperm by a trogocytosis-dependent spermicidal activity independent of neutrophil extracellular traps (NETs). WHAT IS KNOWN ALREADY Trogocytosis has been described as an active membrane exchange between immune cells with a regulatory purpose. Recently, trogocytosis has been reported as a mechanism which PMNs use to kill tumour cells or Trichomonas vaginalis. STUDY DESIGN, SIZE, DURATION We used in vivo murine models and human ex vivo sperm and PMNs to investigate the early PMN–sperm response. PARTICIPANTS/MATERIALS, SETTING, METHODS We set up a live/dead sperm detection system in the presence of PMNs to investigate in vivo and ex vivo PMN-spermicidal activity by confocal microscopy, flow cytometry and computer-assisted sperm analysis (SCA). MAIN RESULTS AND THE ROLE OF CHANCE We revealed that PMNs are highly efficient at killing sperm by way of a NETs-independent, contact-dependent and serine proteases-dependent engulfment mechanism. PMNs ‘bite’ sperm and quickly reduce sperm motility (within 5 min) and viability (within 20 min) after contact. LARGE SCALE DATA N/A LIMITATIONS, REASONS FOR CAUTION This study was conducted using murine models and healthy human blood PMNs; whether it is relevant to human vaginal PMNs or to cases of infertility is unknown. WIDER IMPLICATIONS OF THE FINDINGS Vaginal PMNs attack and immobilize excess sperm in the vagina by trogocytosis because sperm are exogenous and may carry pathogens. Furthermore, this mechanism of sperm regulation has low mucosal impact and avoids an exacerbated inflammatory response that could lead to mucosal damage or infertility. STUDY FUNDING/COMPETING INTEREST(S) This work was partially supported by Ministry of Economy and Competitiveness ISCIII-FIS grants, PI16/00050, and PI19/00078, co-financed by ERDF (FEDER) Funds from the European Commission, ‘A way of making Europe’ and IiSGM intramural grant II-PI-MRC-2017. M.R. holds a Miguel Servet II contract (CPII14/00009). M.C.L. holds IiSGM intramural contract. There are no competing interests.

Sperm modulate uterine immune parameters relevant to embryo implantation and reproductive success in mice

“…Once in the luminal cavity, neutrophils selectively eliminate subsets of sperm by release of NETs 51 and trogocytosis 54 , although the basis of selection remains unclear. Although this is can be viewed as a ‘hostile’ female response to the male gametes 28 , neutrophil-mediated selection of the fittest or most compatible sperm for fertilization may ultimately increase the chances of a given male siring healthy offspring 55 .…”

A Retrospective Analysis of the Correlation between Trichomonas Vaginalis Infection and Infertility

“…The in ammatory response induced by T. vaginalis can cause neutrophilia through serine protease-dependent pathogenesis. Therefore, contact between neutrophils and sperm cells leads to sperm phagocytosis and death [33]. In infertile females with T. vaginalis infection, the levels of C3 and C4 were decreased, while the levels of IgA and serum prolactin in vaginal secretions were increased [34],…”

“…We retrieved 62 research articles, seven of them were selected [12,[28][29][30][31][32][33] based on the inclusion and exclusion criteria.…”

Cross-Talk among Polymorphonuclear Neutrophils, Immune, and Non-Immune Cells via Released Cytokines, Granule Proteins, Microvesicles, and Neutrophil Extracellular Trap Formation: A Novel Concept of Biology and Pathobiology for Neutrophils

“…Mercer et al [144], by using 3D and 4D live imaging, observed that PMNs kill the parasites in a contact-dependent, NET-independent engulfment process with bites prior to parasite death, i.e., trogocytosis. In addition, Olivera-Valle et al [145] watched that PMN "bites" sperm and quickly reduces its motility (<5 min) and viability (<20 min) after contact with it in the vaginal lumen but with a low impact on the mucosa damage. These observations indicate PMNs can act as vaginal patrolmen for keeping vaginal homeostasis.…”