[23, 24] The female reproductive tract and placenta may become exposed to viruses in addition to bacterial or fungal infection, which may pose a substantial threat to reproductive outcome or embryo/fetus well-being. Although studies are limited, it is important to determine the type of virus and whether the engagement of TLR3 with viral dsRNA could induce production of factors necessary to generate an antiviral response. In fact, TLR3 expression has been demonstrated in the epithelial cells of the vagina, uterine cervix, endometrium, fallopian tubes and also in placenta.[11, 27] For most of the reproductive cycle in humans and animals, the

uterus is thought to be sterile or at least clear of pathogenic bacteria, but it is readily contaminated with bacteria during sexual intercourse and around the time of parturition. In fact, Target Selective Inhibitor Library chemical structure the upper genital tract is vulnerable to the spread of microorganisms from the lower genital tract, resulting in the development of infectious diseases such as endometritis and salpingitis. In fact, an enormous Selleck Tanespimycin number of Gram-negative

and Gram-positive microbes are present in the vaginal cavity (Table 2). All these microbes reside in the vaginal cavity as normal vaginal flora and may cause genitourinary infections upon ascending migration.[27] Escherichia coli Proteus vulgaris Klebsiella Enterobacter Escherichia coli Proteus vulgaris Klebsiella Enterobactor Acinetobactor calcoaceitus Pseudomonas aeroginosa Serratia Neisseria gonorrhoeae Bacteroids fragilis Bacteroids urolyticus Pervotella Mobiluncus spp. Bacteroids fragilis Bacteroids urolyticus Pervotella Mobiluncus spp. Porphyromonas Chlamydia

trachomatis Gardnerella vaginalis Enterococci Staphylococcus saproplyticus Staphylococcous aureus Streptococcus faecalis Staphylococcus epidermidis Lactobacillus acidophilus Clostridium Peptostreptococcus Mycoplasma hominis Candida albicans Blastomyces Coccidioides immitis In recent years, increasing attention has been paid to innate immunity, the primary defense system against pathogens. Escherichia coli are the most commonly isolated pathogenic bacteria from clinical uterine diseases in cattle[28] and also in the human vaginal Vildagliptin cavity.[29] The ascending migration of E. coli towards the endometrial cavity possibly may cause contamination of the endometrium. The endometrium provides a barrier against infection and an opportunity to detect these bacteria by innate immune receptors. TLR were first identified on immune cells but have since been identified on other cell types including endometrium.[30] In the human endometrium, nine TLR are identified at the protein and mRNA level including TLR4.[12, 31-33] Engagement of these receptors initiates a signaling cascade stimulating the production of immune mediators that orchestrate the immune response to clear the infection. It is the principal role of TLR4 to detect LPS, although signaling through TLR4 also requires accessory molecules such as LBP, CD14 and MD2.