Submitted to: Electronic Publication
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 28, 2003
Publication Date: November 28, 2003
Citation: Lewis, G.S. 2003. Steroidal regulation of uterine resistance to bacterial infection in livestock. Reproductive Biology and Endocrinology. 1:117. http://www.rbej.com/content/1/1/117. 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 (PGF2LPHA) 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: Postpartum uterine infections reduce reproductive efficiency and have significant animal welfare and economic consequences. Postpartum uterine infections are classified as nonspecific, but Arcanobacterium pyogenes and Escherichia coli are usually associated with them in cattle and sheep. Pyometra is the most common type of uterine infection in dairy cattle, and it is detected almost exclusively in cows with active corpora lutea. Luteal progesterone typically down-regulates uterine immune functions and prevents the uterus from resisting infections. Progesterone also can downregulate uterine eicosanoid synthesis. This seems to be a critical event in the onset of uterine infections, because eicosanoids can up-regulate immune cell functions in vitro. In addition, exogenous prostaglandin F2alpha (PGF2a) stimulates uterine secretion of PGF2a and enhances immune functions in vivo. Thus, one may hypothesize that eicosanoids can override the negative effects of progesterone and that the up-regulatory effects of exogenous PGF2a allow the uterus to resolve an infection, regardless of progesterone concentrations. Based on the results of studies to test that hypothesis, cows, sheep, and pigs in various physiological statuses are resistant to intrauterine infusions of Arcanobacterium pyogenes and Escherichia coli, unless progesterone concentrations are increased. In sheep and pigs, exogenous PGF2a stimulates uterine production of PGF2a and allows the uterus to resolve Arcanobacterium pyogenes-Escherichia coli-induced infections, even when progesterone is maintained at luteal phase concentrations before and after treatment. Prostaglandin F2a is a proinflammatory molecule that stimulates the production of various proinflammatory cytokines, and it may enhance uterine production of leukotriene B4. Proinflammatory cytokines and leukotriene B4 (LTB4) enhance phagocytosis and lymphocyte functions. Even though there are clear associations among PGF2a, LTB4, proinflammatory cytokines, phagocytosis, and lymphocyte functions, the mechanism of action of exogenous PGF2a in overriding the down-regulatory effects of progesterone and resolving uterine infections has not been elucidated. Defining this mechanism should yield new prevention and treatment strategies for uterine infections that do not rely on antibiotic and antimicrobial compounds.