Cytokine‐Leukocyte Networks and the Establishment of Pregnancy

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Abstract
PROBLEM: Factors in seminal plasma stimulate an intense but transient inflammatory response in the murine endometrium at mating. The aim of our current studies is to delineate the cytokine‐leukocyte interactions comprising this response and to elucidate the significance of these events in changes in the maternal immune system and as determinants of pregnancy outcome. METHOD: We have reviewed our recent findings. RESULTS: Transforming growth factor (TGF)‐β1 has been identified as the inflammation‐inducing moiety in seminal plasma. Seminal TGFβ1 initiates endometrial leukocyte infiltration by up‐regulating epithelial cell expression of granulocyte‐macrophage colony‐stimulating factor. Other cytokines and chemokines including regulated and normal T‐cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)‐1α, MIP‐1β, and monocyte chemotactic protein‐1 are also implicated as mediators of macrophage and granulocyte recruitment and activation. One consequence of this inflammatory response is the induction of a transient state of hyporesponsiveness to paternal major histocompatibility class I antigens. CONCLUSION: Our studies suggest that semen may play a critical role in providing the antigenic and environmental signals necessary to initiate an appropriate maternal immune response to the conceptus during pregnancy.