Seminal DNase Frees Spermatozoa Entangled in Neutrophil Extracellular Traps

Insemination always stimulates neutrophil migration into the female reproductive tract (FRT), which eliminates excess spermatozoa and bacterial contaminants introduced by the breeding process. However, the presence of neutrophils in the FRT at the time of semen deposition has been shown to result in sperm-neutrophil binding that reduces motility and fertility. Although the binding and trapping mechanism has not been determined, seminal plasma (SP) was found to include a protein factor or factors that reduced sperm-neutrophil binding and improved fertility of sperm inseminated in the presence of neutrophils. Although DNase has been shown to be present in the SP of different species and has been associated with improved fertility in bulls, the mechanism(s) explaining this association and the paradox of DNA-packed cells being associated with DNase have remained unresolved. We demonstrate that sperm-activated neutrophils extrude their DNA, which in turn traps sperm cells and hinders their motility (and ultimately may hinder sperm transport to the fertilization site). DNase activity present in the SP digests the extruded DNA and frees entangled spermatozoa, which in turn may allow more spermatozoa to reach the oviduct, and explains at least one mechanism by which SP increases the rate of fertility. The ability of SP proteins to suppress neutrophil activation in the presence of spermatozoa did not render neutrophils incapable of combating bacteria, demonstrating that SP proteins are highly selective for suppressing neutrophils activated by spermatozoa, but not by bacteria.