Seminal transforming growth factor β₁ 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 colony-stimulating 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 β₁ (TGFβ₁) in the 150- 440-kDa range and was neutralized by anti-TGFβ₁ antibodies. Comparable amounts of recombinant TGFβ₁ 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 TGFβ₁ 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 TGFβ₁ 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.