Actions of Seminal Plasma Cytokines in Priming Female Reproductive Tract Receptivity for Embryo Implantation

Abstract

Embryo implantation is critically dependent on a supportive uterine environment. Uterine receptivity is the culmination of a cellular and molecular transformation mediated locally by paracrine signals under the governance of ovarian steroid hormones, with cells and cytokines of the immune system playing integral roles in this process. Semen is now recognised as contributing to endometrial preparation for embryo implantation, through the agency of specific factors in the seminal plasma fraction of the ejaculate. Transforming growth factor-$β$ (TGF$β$) and other immunoactive moieties derived from male accessory glands interact with epithelial cells in female reproductive tissues to induce pro-inflammatory cytokine expression and initiate an inflammatory cascade. The consequences are recruitment and activation of macrophages, granulocytes and dendritic cells which have immune-regulatory and tissue remodelling roles. The cytokines elicited by seminal activation also exert embryotrophic effects and contribute to optimal preimplantation embryo development. This review summarises our current understanding of the molecular and cellular basis of interactions between seminal plasma and the female reproductive tract, and explores the potential mechanisms through which seminal plasma influences the establishment of pregnancy.