Immune cell–endothelial cell interactions in the bovine corpus luteum

Early embryonic mortality accounts for a substantial portion of reproductive failure in agriculturally important livestock, including the dairy cow. The maintenance of early pregnancy requires a fully functional corpus luteum (CL) that is not susceptible to regression following fertilization, yet the cellular mechanisms of luteal regression are not clearly understood. Immune-cell accumulation within the CL at the time of regression is a well-documented phenomenon in a variety of species. In the dairy cow, immune-cell accumulation precedes luteal regression by several days and coincides with an increase in expression of the chemokine monocyte chemoattractant protein 1 (CCL2), suggesting that immune-mediated events promote tissue destruction. Recent studies indicate that endothelial cells comprising the CL are a primary source of CCL2 secretion. Moreover, although uterine-derived prostaglandin F2α (PGF) initiates luteal regression in the cow, PGF does not directly provoke CCL2 secretion by luteal endothelial cells. Instead, PGF-induced luteal regression is thought to require cooperative interaction among immune cells, endothelial cells, and steroidogenic cells of the CL to further promote CCL2 secretion, enhance immune-cell recruitment, and eliminate luteal tissue. This brief review focuses on putative interactions between immune cells and endothelial cells derived from the bovine CL that result in enhanced CCL2 expression and the elaboration of other inflammatory mediators (for example, cytokines), which perpetuate luteal regression. Fundamental knowledge of immune-endocrine interactions within the reproductive system of cows has relevance to other CL-bearing mammals, including humans and endangered animals, particularly in the development of methods to control and/or improve fertility. Thus, it is a timely topic for this symposium concerning ecological immunology and public health.