Paternal health before conception is critical for pregnancy outcome and infant health, yet the mechanisms remain underexplored. Accumulating evidence shows bioactive factors in seminal fluid are sensitive to environmental cues, and can modulate endometrial receptivity to in turn shape fetal development. Given emerging viral threats, we sought to investigate how peri-conceptional paternal anti-viral immune activation affects seminal fluid components and subsequent pregnancy.
Here, we administered a synthetic viral RNA mimetic (polyinosinic:polycytidylic acid; poly I:C) that induces inflammation through toll-like receptor 3 activation. To assess the acute impact of poly I:C on male reproductive function, C57Bl/6 male mice were treated with 10mg/kg poly I:C or vehicle, followed by sperm motility assessment by computer-assisted semen analysis at 0h, 6h, 12h and 24h post-treatment. Pro-inflammatory cytokine gene expression was measured in seminal vesicles by qPCR at the same timepoints. Poly I:C- or vehicle-treated males were mated with BALB/c females on the night of treatment, and fetal outcome was assessed at late gestation on day 17.5 post-coitum.
Poly I:C increased pro-inflammatory Ccl2, Il6, Ifng and Tnf expression in seminal vesicles at 6 hours post-treatment (>6-fold increase, n=4-5/group, p<0.05). Although pregnancy rate, implantation rate and fetal viability in late gestation were comparable between groups, fetal weight was reduced by 6.5% in poly I:C-sired pregnancies, accompanied by decreased fetal:placental weight ratio indicating decreased placental efficiency (n=11-15 dams/group, p<0.05). Sperm parameters were not affected at 24 hours after poly I:C treatment, suggesting impaired fetal growth may be due to altered seminal plasma composition and effects on endometrial receptivity.
Collectively, these findings indicate that peri-conceptional paternal viral infection may dysregulate seminal fluid molecular composition, with potential to adversely affect fetal growth. Future experiments will examine the underlying mechanisms driving suboptimal pregnancy, which will provide insights into potential therapeutic strategies to mitigate impaired fetal growth caused by paternal infection.