Successful reproduction depends on far more than fertilization alone. Our laboratory investigates how stallion sperm and seminal plasma actively influence the mare’s reproductive tract, early pregnancy establishment, and long-term reproductive success. We study the molecular composition of seminal plasma—including cytokines, extracellular vesicles, metabolites, and other bioactive molecules—and how these signals regulate sperm function, uterine immunity, and maternal recognition of pregnancy. In parallel, our work examines the biology of sperm themselves, exploring how they respond to bacterial pathogens, environmental stressors, and inflammatory stimuli, including the emerging concept that sperm may actively participate in immune signaling through the production of cytokines, or “spermikines.” We also investigate the effects of seminal plasma on sperm longevity, motility, mitochondrial function, capacitation, and fertilization potential, while identifying factors that promote a healthy uterine environment following breeding. By integrating reproductive physiology, immunology, proteomics, and molecular biology, our research seeks to redefine the role of sperm and seminal plasma as dynamic mediators of communication between the stallion and mare. Ultimately, this work aims to improve fertility, optimize assisted reproductive technologies, and advance our understanding of the complex biological interactions that support successful pregnancy in horses while providing insights relevant across mammalian species.