Response to a study on prostaglandins and bacterial growth in endometriosis

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Study:

“Role of prostaglandin E2 in bacterial growth in women with endometriosis

Abstract

STUDY QUESTION Can prostaglandin E2 (PGE2) in menstrual and peritoneal fluid (PF) promote bacterial growth in women with endometriosis?

SUMMARY ANSWER PGE2 promotes bacterial growth in women with endometriosis.

WHAT IS KNOWN ALREADY Menstrual blood of women with endometriosis is highly contaminated with Escherichia coli (E. coli) compared with that of non-endometriotic women: E. coli-derived lipopolysaccharide (LPS) promotes the growth of endometriosis.

STUDY DESIGN, SIZE AND DURATION Case-controlled biological research with a prospective collection of body fluids and endometrial tissues from women with and without endometriosis with retrospective evaluation.

PARTICIPANTS/MATERIALS, SETTING AND METHODS 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. The exogenous effect of PGE2 on the replication of E. coli was examined in a bacterial culture system. Levels of PGE2 in different body fluids and in the culture media of Mφ and stromal cells were measured by ELISA. The effect of PGE2 on the growth of peripheral blood lymphocytes (PBLs) was examined.

MAIN RESULTS AND THE ROLE OF CHANCE The 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. PGE2-enriched MF was able to stimulate the growth of E. coli in a dilution-dependent manner; this effect was more significantly enhanced in women with endometriosis than in control women (P < 0.05). PGE2 levels in the culture media of LPS-treated Mφ/stromal cells were significantly higher in women with endometriosis than in non-endometriosis (P < 0.05 for each). Direct application of PGE2and culture media derived from endometrial Mφ or stromal cells significantly suppressed phytohemagglutinin-stimulated growth of PBLs.

LIMITATIONS AND REASONS FOR CAUTION 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 Our findings may provide some new insights to understand the physiopathology or pathogenesis of the mysterious disease endometriosis and may hold 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.”

Dr Redwine’s Response:

“Here is my interpretation of the study: prostaglandin E2 (PGE2) is a chemical produced by the body as part of the body’s inflammatory response. Women with endometriosis have chronic inflammation due to their disease – the inflammation may wax and wane with hormonal changes throughout the month – so women with endometriosis have more PGE2 production than women without endometriosis. PGE2 can be produced wherever there is inflammation, so in women with endometriosis, it is found in increased levels in the peritoneal fluid. PGE2 can also be found in increased levels in the uterus and in the menstrual fluid. It is possible that this increased level of PGE2 in the uterus and menstrual fluid may be a result of inflammation of the uterus due to something affecting it primarily (such as occult adenomyosis) or secondarily (such as widespread pelvic inflammation due to endometriosis). e coli bacteria are a normal inhabitant of the vagina in all women. Menstrual fluid passing through the vagina picks up the e coli which is normally there, so e coli can be cultured from the menstrual fluid. Women with endometriosis have been found to have a higher level of colonization of e coli in the menstrual fluid than women without endometriosis. This study sought to figure out why this occurs. Part of the answer may relate to increased levels of PGE2 in women with endometriosis. The investigators added PGE2 to e coli in a petri dish and found that this made the e coli grow more readily. Therefore, increased levels of PGE2 which occur as a normal response to inflammation may be the explanation for heavier growths of e coli in the menstrual fluid of women with endometriosis. The study says nothing about whether women with endometriosis are more prone to pelvic infections with e coli or any other bacterium than women without endometriosis. Pelvic infection in women with endometriosis is not common. However, there are occasional case reports of an infected endometrioma cyst of the ovary turning into an abscess. It is possible that increased PGE2 production may have played a role in such cases by promoting the growth of bacteria. Keep in mind that PGE2 is only one of several inflammatory chemicals produced in response to inflammation, so there may be some contribution by other inflammatory chemicals as well. Nothing about this study suggests that women with endometriosis have decrepit immune systems.”