The molecular pathophysiology of bacterially induced preterm labor: insights from the murine model.

Premature delivery, the most important problem in obstetrics in developed countries, continues to vex clinicians and researchers. Despite decades of investigation, the pathophysiology of premature labor is incompletely understood, and therapies or preventive strategies tailored to each of the many potential causes do not exist. The present review addresses one cause of prematurity, namely, intrauterine bacterial infection. Given the vastness of the literature for even this single etiology, we focus on the mouse as a model organism from which much can be learned about mammalian parturition. The underpinnings of bacterially induced labor are believed to involve a signaling cascade that begins with recognition of offending pathogens by cell-surface receptors (toll-like receptors). This cascade then operates through multiple branching and redundant pathways to bring about the changes within the gestational compartment that produce cervical ripening, labor, and ultimately delivery. The major challenge facing researchers is to understand the levels of complexity in the host response, so that prevention and treatment strategies may be sufficiently focused to minimize unwanted side effects, yet sufficiently broad to be effective. Given the complexity of the problem, this understanding can be aided by efficient model systems, of which one in vivo example is the mouse, an organism that shares with humans many similarities in the biochemical and molecular aspects of inflammation-induced preterm labor. We propose that tools with the power to assess simultaneously the myriad elements of the hypothesized signaling cascade (ie, genomic and proteomic technologies) are important components of the solution to the puzzle of parturition.