Seminal transforming growth factor beta1 stimulates granulocyte- macrophage colony-stimulating factor production and inflammatory cell recruitment in the murine uterus

Mating in rodents evokes an inflammatory-like reaction within the uterine endometrium, characterized by extensive infiltration and activation of macrophages, dendritic cells, and granulocytes. This response is initiated when seminal vesicle gland-derived factors in the ejaculate stimulate uterine epithelial cells to release proinflammatory cytokines including granulocyte-macrophage colonystimulating factor (GM-CSF). Experiments in which seminal vesicle secretions were fractionated by Sephacryl S-400 chromatography and assayed in vitro for GM-CSF-stimulating activity revealed that the seminal moiety coeluted with transforming growth factor (beta)1 (TGF(beta)1) in the 150-440-kDa range and was neutralized by anti-TGF(beta1) antibodies. Comparable amounts of recombinant TGF(beta)1 stimulated GM-CSF release in cultures of uterine epithelial cells from estrous mice and, when instilled into the uterine lumen, caused an increase in GM-CSF content and an infiltration of leukocytes into the endometrium similar to the postmating response. These results show that seminal vesicular fluid contains TGF(beta1) at levels sufficient to be the primary causative agent in the postmating inflammatory cascade through induction of GM- CSF synthesis by uterine epithelial cells. Seminal TGF(beta1) is thus implicated as a key factor in initiation of the remodeling events and immunological changes that occur in the uterus during the preimplantation period of pregnancy.