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The human lower genital tract is constantly exposed to various microorganisms, which can infect the upper genital tract through ascending migration. We report on tests of the hypothesis that as normal microbial flora in the vagina, some gram-negative bacteria infect the uterine wall after ascending migration from the vagina, to contaminate menstrual blood, consequently resulting in accumulation of endotoxin in the menstrual/peritoneal fluid and initiation of pelvic inflammation. The aim of the present review is to assess possible intrauterine microbial colonization and to examine the stimulatory effect of E. coli-derived lipopolysaccharide (LPS) on the secretion of various macromolecules by macrophages (Mφ) known to be involved in endometriosis. We also assess the growth-promoting effect of LPS on endometrial cells and the role of Toll-like receptor 4 (TLR4), a receptor recognizing LPS, in the secretion of macromolecules by Mφ and growth of endometrial cells. We found higher intrauterine microbial colonization in women with endometriosis than in controls. The ligand from gram-negative bacteria is involved in TLR4-mediated proinflammation in the pelvis as well as growth of endometriosis. Treatment with gonadotropin-releasing hormone agonist (GnRHa) further promotes intrauterine microbial colonization compared with GnRHa-untreated women.We propose the bacterial contamination hypothesis as a new concept in endometriosis. Based on our current findings, an estrogen-suppressing agent and an antimicrobial agent may have new therapeutic potential in women with endometriosis.