Figure 2.

Immunomodulation of SP factors in the maternal reproductive tract to facilitate early embryo development and implantation. Seminal plasma contains chemokines, cytokines, and prostaglandins produced by Leydig and Sertoli cells, seminal vesicles, leukocytes, and other immune cells present in the male reproductive tract. These factors potentially induce inflammation, immunotolerance, and angiogenesis to support embryo development and implantation through the upregulation of embryokines, chemokines, and cytokines from oviductal and uterine tissues. Binding of active moieties in SP to endothelial cells stimulates the recruitment of neutrophils into the uterine tissues, which can clear up excess sperm and seminal debris. Moreover, dendritic cells can recognize paternal major histocompatibility antigens and pass them onto naive T cells and generate an expanded T regulatory (Treg) cell pool in lymph nodes. Since the embryo presents the same paternal antigens in the SP, the response of Tregs to these antigens can be efficiently suppressed, which allows implantation of the semiallogenic embryo into the maternal uterine. On the other hand, Tregs also contribute to endometrial tissue remodeling and receptivity for implantation through the regulation of angiogenesis. SP also results in the production of cytokines and growth factors, such as colony-stimulating factors (CSFs), leukemia inhibitory factor (LIF), and interleukin 6 (IL-6), by the maternal reproductive tract, which are essential for promoting embryo development before implantation. The arrow indicates that embryotrophic factors (CSF1, CSF2, CSF3, IL6, VEGF) are induced by SP during the early embryonic development.