Cytokine-leukocyte networks and the establishment of pregnancy.

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)-beta1 has been identified as the inflammation-inducing moiety in seminal plasma. Seminal TGFbeta1 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)-1alpha, MIP-1beta, 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.