Submitted to: Animal Reproduction Science
Publication Type: Peer reviewed journal
Publication Acceptance Date: 3/15/2004
Publication Date: 4/1/2004
Citation: Lewis, G.S. 2004. Steroidal regulation of uterine immune defenses. Animal Reproduction Science. 82-83:281-294. Interpretive Summary: Progesterone seems to be the primary ovarian steroid that governs the ability of the uterus to resist infections. In livestock, progesterone typically down-regulates immune functions and makes the uterus susceptible to infections. Exogenous prostaglandin F2alpha (PGF2alpha) increases uterine secretion of PGF2alpha, and probably leukotriene B4, and these two eicosanoids are associated with enhanced uterine immune responses and resistance to infections. Even though progesterone and eicosanoids affect a variety of proinflammatory molecules that can alter uterine immune responses, the role of these molecules in determining whether the uterus in livestock is resistant or susceptible to infections has not been elucidated. Indeed, determining how uterine PGF2alpha is able to stimulate the uterus to resolve infections, even when progesterone concentrations are increased, should be important to scientists and clinicians working to understand the underlying causes of uterine infections. Information from this line of research should yield important new prevention and treatment strategies for uterine infections that do not rely on antibiotic and antimicrobial compounds.
Technical Abstract: Progesterone suppresses uterine immune defenses and predisposes postpartum animals to nonspecific uterine infections. Progesterone can also suppress the synthesis of uterine eicosanoids. This effect of progesterone seems to be an important factor in the onset of uterine infections because eicosanoids can enhance uterine immune defenses. In fact, exogenous prostaglandin F2alpha (PGF2lpha), an eicosanoid that stimulates uterine PGF2alpha production, enhances uterine immune defenses and promotes the ability of ewes and sows to resolve uterine infections, even when progesterone is maintained at luteal phase concentrations. Prostaglandin F2alpha is also a proinflammatory molecule that stimulates the production of proinflammatory cytokines and may enhance uterine production of leukotriene B4 (LTB4), which stimulates various neutrophil functions. Neutrophils seem to mount the initial response to bacteria that enter the uterus, and proinflammatory cytokines and LTB4 enhance phagocytic activity of neutrophils. Even though there are clear associations among PGF2alpha, LTB4, proinflammatory cytokines, phagocytosis, and the ability of the uterus to resist or resolve infections, the mechanisms of action of exogenous PGF2' in mitigating the immunosuppressive effects of progesterone have not yet been defined. However, defining the PGF2' mechanisms should yield important new information that can be used to develop novel prevention and treatment strategies that do not rely on antibiotic and antimicrobial compounds for managing uterine infections.