New models of lipopolysaccharide-induced implantation loss reveal insights into the inflammatory response.

problemChronic endometritis, inflammation of the uterizzvvne lining caused by common gram-negative bacterial strains or mycoplasma, has been associated with unexplained implantation failure and infertility. However, limited models of bacteria-induced implantation loss exist to study the molecular changes that occur in vivo. The goal of this study was to provide a new resource to study the process of bacteria-induced inflammation and implantation loss utilizing common experimental models: C57Bl/6 mice and primary human endometrial stromal cells. METHOD OF STUDY: Prior to implantation, mated C57Bl/6 females were administered vehicle (saline) or gram-negative bacterial lipopolysaccharide (LPS) at a range of concentrations by intraperitoneal injection. Implantation sites were counted, and uteri were harvested to evaluate the molecular changes that accompany LPS-mediated implantation loss. Primary human endometrial stromal cells were decidualized in vitro in the presence and absence of LPS. Total RNA and conditioned media were harvested to evaluate the expression of known decidualization-associated genes and various cytokines and chemokines.

resultsLipopolysaccharide treatment resulted in fewer implantation sites in mice, decreased expression of decidualization-associated genes, and altered expression and release of cytokines and chemokines. Immunohistological analysis of the uterus from LPS-exposed mice demonstrated increased apoptosis and decreased proliferation during decidualization.

conclusionLipopolysaccharide exposure disrupted implantation and decidualization in mice and human endometrial stromal cells. This model could be used to study the pathophysiology of implantation failure in patients with chronic endometritis or to test potential therapeutic interventions.