Sperm induce macrophages extracellular trap formation via phagocytosis -dependent mechanism

Infertility is a public health concern worldwide. Asthenozoospermia (AZS) is a common cause of male infertility and is characterized by decreased motility due to abnormal morphology of sperm flagella. Sperm motility ensures that sperm migrate from the vagina to the fallopian tube to complete fertilization. Macrophages are an essential component of innate immunity in the female reproductive tract. Macrophage extracellular traps (METs) are induced by various Microorganisms to capture and mediate the clearance of Microorganisms. The relationship between sperm and METs is unclear. THP-1 cells differentiated by phorbol myristate acetate (PMA) are widely used as surrogate of human macrophages. This study investigated sperm-induced METs formation in PMA-differentiated THP-1 macrophages co-incubated with sperm and clarified some of the mechanisms affecting METs production. Sperm-induced METs were visualized and components of METs were identified by immunofluorescence analyses and scanning electron microscopy (SEM). By inhibiting METs production and macrophage phagocytosis, the relationship between macrophage phagocytosis and METs production was analyzed. Sperm could trigger PMA-differentiated THP-1 macrophages to produce extracellular traps. Sperm-triggered METs are dependent on phagocytosis and NADPH Oxidase. Sperm from asthenozoospermia donors is more likely to be phagocytosed by macrophages than sperm from healthy donors, which induce more METs release to capture and immobilize sperm. These data confirm the phenomenon and partial mechanism of sperm-induced METs formation in vitro. These may partly provide evidence to explain the mechanisms of clearing abnormally morphological or hypomotility sperm in the female reproductive tract and the rationale for the decreased probability of successful fertilization in asthenozoospermia.

Asthenozoospermia; Macrophage extracellular traps (METs); Phagocytosis; Sperm; Sperm motility.