SEMINAL TRANSFORMING-GROWTH-FACTOR BETA(1) 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 uter ine endometrium, characterized by extensive infiltration and activatio n 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 cytokine s 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-stimula ting activity revealed that the seminal moiety coeluted with transform ing growth factor beta(1) (TGF beta(1)) in the 150-440-kDa range and w as neutralized by anti-TGF beta(1) antibodies. Comparable amounts of r ecombinant TGF beta(1) stimulated GM-CSF release in cultures of uterin e epithelial cells from estrous mice and, when instilled into the uter ine lumen, caused an increase in GM-CSF content and an infiltration of leukocytes into the endometrium similar to the postmating response. T hese results show that seminal vesicular fluid contains TGF beta(1) at revels sufficient to be the primary causative agent in the postmating inflammatory cascade through induction of GM-CSF synthesis by uterine epithelial cells. Seminal TGF beta(1) is thus implicated as a key fac tor in initiation of the remodeling events and immunological changes t hat occur in the uterus during the preimplantation period of pregnancy .