ROLE OF HIGH-MOLECULAR-WEIGHT SEMINAL-VESICLE PROTEINS IN ELICITING THE UTERINE INFLAMMATORY RESPONSE TO SEMEN IN MICE

Mating evokes a characteristic pattern of molecular and cellular event s in the rodent reproductive tract, including an infiltration of the e ndometrial stroma and uterine lumen with activated macrophages and gra nulocytes, which closely resembles a classic inflammatory response. Pr evious studies in mice indicate that these cellular changes are associ ated with, and are largely a consequence of, an upregulated synthesis and release of granulocyte-macrophage colony-stimulating factor (GM-CS F) from the uterine epithelium in response to seminal fluid. The aim o f this study was to investigate further the origin and nature of the f actors present in seminal fluid that trigger the GM-CSF response. It w as found that the characteristic increase in uterine expression of mRN A encoding GM-CSF and release of GM-CSF bioactivity from uterine epith elial cells into the luminal cavity seen after mating with intact or v asectomized males was no longer evident in matings with male mice from whom the seminal vesicles had been surgically removed. The extent of inflammatory leucocyte infiltration into the endometrium was also redu ced; the most notable effect was a complete absence of the exocytosis of neutrophils into the luminal cavity normally seen after matings wit h intact or vasectomized males. Bioassay of the GM-CSF output of oestr ous endometrial cells after culture with crude or Sephacryl S-400 chro matographed fractions of seminal vesicle fluid showed that the GM-CSF stimulating activity was predominantly associated with protein moietie s in seminal vesicle fluid of approximately 650 000 M(r) and 100 000-4 00 000 M(r). These data confirm the presence in seminal vesicle fluid of specific factors that initiate an inflammatory response in the uter us after mating through upregulating GM-CSF synthesis in the uterine e pithelium. The significance of the cytokine release and cellular chang es induced by seminal plasma for implantation of the conceptus and pre gnancy outcome remain to be determined.