Seminal fluid cytokines in reproductive health and fertility of men

Seminal fluid is more than a vehicle for sperm transport. It contains a complex mix of immune-regulatory cytokines that, together with other bioactive factors, influence sperm maturation and survival, and interact with female reproductive tract cells and tissues to facilitate conception and stimulate female receptivity to pregnancy. Cytokines synthesized in the seminal vesicles, prostate, and other male accessory glands come into contact with sperm at ejaculation, and upon intromission are delivered to the cervix and uterus in soluble form, as cargo of seminal extracellular vesicles, or in physical association with sperm. The relative concentrations of different cytokines vary between individual men and can fluctuate over time - in response to local and systemic viral or bacterial infection, acute and chronic inflammatory and metabolic disorders, such as varicocele, prostatitis and diabetes, and environmental exposures including heat stress, chemical toxin exposures, and smoking. Although seminal fluid cytokines in healthy men promote fertility through permissive effects on embryo development and implantation, elevated abundance of certain proinflammatory cytokines is linked with infertility and subfertility. Emerging insight on the identity and biological functions of key permissive and inhibitory seminal fluid cytokines indicates potential clinical applications in evaluating and managing male and female infertility, and for developing improved assisted reproduction techniques. However, knowledge gaps on the significance of cytokines in reproductive biology and pathophysiology, the most informative cytokines to measure and their normal ranges, and technical challenges regarding optimal assay platforms and protocols, first must be overcome.