Background 

Inflammation and autoimmunity are tightly regulated in the male reproductive tract by T regulatory (Treg) cells. Seminal fluid provides sperm and molecular signals that interact with female tissues to regulate receptivity to pregnancy. Reduced T cell tolerance in males is associated with autoimmunity to sperm antigens, compromising sperm quality. Whether Treg cells also influence seminal plasma composition remains unknown.    

Methods 

Foxp3DTR mice were used to achieve transient acute depletion of Treg cells and assess effects on seminal fluid quality. Foxp3DTR males were mated to clear seminal fluid, then 12 h later (assigned D0), mice received 50 ng/g diphtheria toxin (DT) on D0 and D2 to deplete Treg cells, or PBS control.  

Results 

T cells were analysed in testes, epididymis, testis-draining lymph nodes and spleen using flow cytometry between D4 and D7 (4-7 days post first DT administration) (n=5-7 mice/group). A >95% decrease in total Treg cells, >2-fold increase in activated CD8+ T cells, and >95% decrease in the Treg to T conventional cell ratio was observed in all tissues post-DT administration (all P<0.05). Similar effects were evident across all D4-D7 time points examined. 

DT administration caused a 15.5% and 28.6% decrease in the weight of seminal vesicles and volume of recovered seminal vesicle fluid respectively (both P<0.05). Acute Treg cell depletion did not affect number of epididymal sperm or motility parameters measured using computer-assisted sperm analysis (n=8-12 mice/group).  

Conclusion 

Foxp3DTR mice provide a useful model to examine fertility effects of short-term Treg cell deficiency in male mice. A protocol was developed to allow examination of effects on seminal vesicles under circumstances where sperm parameters are unaffected. Initial observations show altered seminal vesicle weight and fluid secretions after acute Treg cell depletion. These data suggest that Treg cells may be an important determinant of male seminal fluid quality.