Role of prostaglandin E2 in bacterial growth in women with endometriosis

Khan KN et al., Page 2 Title: Role of prostaglandin E2 in bacterial growth in women with endometriosis. Study question: To investigate the role of bacteria in endometriosis. Summary answer: Prostaglandin (PG) E2 in involved in the bacterial growth in women with endometriosis. What is known already: Menstrual blood of women with endometriosis is highly contaminated with Escherichia coli (E.coli) than in non-endometriosis and E.coli-derived lipopolysaccharide (LPS) promotes the growth of endometriosis. Study design, size and duration: This is a case-controlled biological research with prospective collection of body fluids and endometrial tissues from women with and with endometriosis and retrospective evaluation. Participants/materials, setting, methods: Peritoneal fluid (PF) and sera were collected from 58 women with endometriosis and 28 women without endometriosis in an academic research laboratory. Menstrual blood was collected from a proportion of these women. Macrophages (Mφ) from PF and stromal cells from eutopic endometria were isolated in primary culture. Exogenous effect of PGE2 on the replication of E.coli was examined in a bacteria culture system. Levels of PGE2 in different body fluids and in the culture media Khan KN et al., Page 3 of Mφ and stromal cells was measured by ELISA. Effect of PGE2 on the growth of peripheral blood lymphocytes was examined. Main results and the role of chance: PGE2 level was 2-3 times higher in the menstrual fluid (MF) than in either sera or in PF. A significantly higher level of PGE2 was found in the MF and PF of women with endometriosis than in control women (p<0.05 for each). Exogenous treatment with PGE2 dose-dependently increased E.coli colony formation when compared with non-treated bacteria. Prostaglandin E2-enriched MF was able to stimulate the growth of E.coli in a dilution-dependent manner and this effect was significant in women with endometriosis than in control women (p<0.05). PGE2 levels in the culture media of LPS-treated Mφ/stromal cells was significantly higher in women with endometriosis than in non-endometriosis (p<0.05 for each). Direct application of PGE2 and culture media derived from Mφ or stromal cells were able to significantly suppress phytohemagglutinin (PHA)-stimulated growth of peripheral blood lymphocytes. A higher PGE2 level in the menstrual fluid of women with endometriosis may be involved in the growth of E.coli either by its direct growth promoting effect or by its indirect immunosuppressive effect. Khan KN et al., Page 4 Limitations, reasons for cautions: Further studies are needed to examine the association between PGE2-stimulated growth of E.coli and endotoxin level and to investigate the possible occurrence of sub-clinical infection within vaginal cavity. Wider implications of the findings: Still claiming as a mysterious disease, our findings may provide some new insights to understand the physiopathology or pathogenesis of endometriosis and may have new therapeutic potential. Study funding/competing interest(s): This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Sports, Culture, Science and Technology of Japan. There is no conflict of interest related to this study. Trial registration number: not applicable.