Cytokine-leukocyte networks and the establishment of pregnancy

Sarah A. Robertson, Vicki J. Mau, Sarah N. Hudson, Kelton P. Tremellen

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139 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)438-442
Number of pages5
JournalAmerican Journal of Reproductive Immunology
Issue number6
Publication statusPublished - Jun 1997
Externally publishedYes


  • GM-CSF
  • Macrophage
  • Seminal plasma
  • TGFβ tolerance
  • Uterus


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