The maternal immune response to semen: implications for reproductive success in livestock

Following semen deposition, the female reproductive tract must balance immune tolerance towards spermatozoa with preservation of antimicrobial defence. To date, much of our understanding of female immune response following insemination has been derived from models of pathogen defence and uterine receptivity in humans, with comparatively little on how these same immune pathways shape successful sperm transport. Here, we summarise the relationship between early sperm transport immediately following semen deposition and acute innate immune activation, characterised by complement engagement and rapid leukocyte recruitment. Polymorphonuclear neutrophils, traditionally viewed as terminal effectors of sperm clearance, are reframed as active mediators of innate surveillance and sperm immune adaptation. Spermatozoa enter the female environment bearing a molecular identity shaped by testicular development, epididymal maturation, and exposure to seminal plasma, yet the link between specific mediators, immunity, and fertility has yet to be explored in livestock. Seminal plasma extracellular vesicles stand out as a promising mediator of complement activity and cytokine signalling. Disruption of this male-derived immune conditioning through processing for cryopreservation is hypothesised to explain impaired sperm transport in sheep. Orchestrating male and female contributions to the maternal immune response reframes reproductive success as coordinated sperm-immune communication. This review identifies knowledge gaps whose resolution will advance our understanding of immune tolerance to spermatozoa, informing strategies to enhance the success of assisted reproductive technologies in livestock.

Successful reproduction requires a highly functional immune response to defend against pathogens while facilitating sperm transport. This review explores how sperm and seminal plasma actively communicate with the female immune system immediately following semen deposition. We highlight how immune cells and complement proteins shape sperm survival, and how alterations to the sperm immune profile during in vitro processing may disrupt this delicate balance of communication within the female.