In the U.S., approximately 300,000 infants are born each year with the biologic disadvantages of prematurity and immaturity. Ten to twenty percent will die within the first year and survivors will suffer serious short- and long-term medical problems. In addition to staggering medical costs, preterm birth causes immense personal, familial and societal costs which arc measured in grief, disability, and lost human potential. Recently Trichomonas vaginalis infection during pregnancy was identified as a significant risk factor for preterm birth arid specifically for pPROM. It is not known how this protozoan parasite damages membranes or predisposes to pPROM. The general goal of this proposal is to develop an in vitro model for pPROM caused by. this protozoan parasite and to identify the pathogenic mechanism of T. vaginalis. We hypothesized that T. vaginalis may impair human fetal membrane strength by production and release of soluble virulence factors and membrane damaging enzymes such as phospholipases or proteases. These virulence factors may mediate weaning by direct attack on constituent component of the fetal membranes including collagen, elastin and fibronectin. The specific goals are to perform histology and electron microscopy on membrane samples delivered from patients with pPROM and on control membrane samples to determine the fate of collagen fibers, elastin fibers and the fibronectin molecule of the extracellular matrix surrounding the cells of the membranes. The second goal is to biochemically characterize pPROM membranes with respect to non-specific protease activity, protease inhibitors, collagenases, and elastases. The third goal is to develop an in vitro model of pPROM caused by Trichomonas vaginalis and look at the effect of parasite proteases and phospholipases on fetal membrane components, collagen, elastin, and fibronectin; and look at the ability of the parasite to functionally weaken the strength of membranes. The strength of fetal membranes will be measured with a dynamometer and the parameters of work to rupture, bursting tension, elasticity and plasticity determined. These in vitro results will be compared to the in vivo data to validate the in vitro model and to facilitate the understanding of the mechanisms of pPROM. The final goal is to further validate the in vitro model with protection studies using protease and phospholipase inhibitors and antibodies to combat virulence factors. Mechanisms of Trichomonal virulence will likely yield paradigms for other sexually transmitted pathogens as we develop a better understanding of the pathogenic interactions of T. vaginalis and gestational tissues, it is hoped that significant progress in the prevention and treatment of STD microorganism induced prematurely can be attained.
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