The male has generally been viewed as having one key function in the reproductive process – to provide a single sperm to fertilize the oocyte. However, studies indicate the male contribution is more complex with effects of seminal fluid influencing pregnancy success and contributing to subsequent fetal development and offspring health. Critical to the female response to seminal fluid is the establishment of a tolerogenic immune environment, dependent on regulatory T cells (Treg cells) raised against paternal antigens, whose functions are to suppress inflammation and immune rejection responses. Factors in the seminal plasma fraction including TGFβ family members have been identified as key signalling agents, but these don’t fully account for the female response. Our research is focused on identifying novel signalling molecules in seminal fluid and determining their impact on the reproductive process. Key signalling factors we have identified include the TLR4 signalling pathway, which is activated by molecules in seminal fluid at coitus and is required for the induction of the key peri-conception cytokines Csf3, Cxcl2, Il6 and Tnf at coitus. Additionally, our studies have demonstrated that components of sperm are required for the complete female response to seminal fluid at coitus and are also involved in the induction of immune-regulatory miRNAs, including miR223. Of these miRNAs, we have demonstrated that miR223 contributes to the expansion of Treg cells following coitus and a deficiency in this miRNA alters pregnancy outcomes. As events around the time of conception have a profound impact over the course of pregnancy, a comprehensive understanding of seminal fluid function can increase our understanding of how infertility, miscarriage and disorders of pregnancy arise, and how the health of the child after birth has origins arising from both maternal and paternal determinants.