Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Hum Reprod. 2012 Dec;27(12):3417-24. doi: 10.1093/humrep/des331. Epub 2012 Sep 20.
Can prostaglandin E(2) (PGE(2)) in menstrual and peritoneal fluid (PF) promote bacterial growth in women with endometriosis?
PGE(2) promotes bacterial growth in women with endometriosis.
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 PGE(2) on the replication of E. coli was examined in a bacterial culture system. Levels of PGE(2) in different body fluids and in the culture media of Mφ and stromal cells were measured by ELISA. The effect of PGE(2) on the growth of peripheral blood lymphocytes (PBLs) was examined.
The PGE(2) level was 2-3 times higher in the menstrual fluid (MF) than in either sera or in PF. A significantly higher level of PGE(2) was found in the MF and PF of women with endometriosis than in control women (P < 0.05 for each). Exogenous treatment with PGE(2) dose dependently increased E. coli colony formation when compared with non-treated bacteria. PGE(2)-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). PGE(2) 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 PGE(2) and culture media derived from endometrial Mφ or stromal cells significantly suppressed phytohemagglutinin-stimulated growth of PBLs.
Further studies are needed to examine the association between PGE(2)-stimulated growth of E. coli and endotoxin level and to investigate the possible occurrence of sub-clinical infection within vaginal cavity.
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.
Not applicable.
月经和腹腔液(PF)中的前列腺素 E(2)(PGE(2))是否会促进子宫内膜异位症患者的细菌生长?
PGE(2)促进子宫内膜异位症患者的细菌生长。
与非子宫内膜异位症女性相比,子宫内膜异位症女性的月经血中高度污染有大肠杆菌(E. coli):大肠杆菌衍生的脂多糖(LPS)促进子宫内膜异位症的生长。
研究设计、大小和持续时间:具有前瞻性收集子宫内膜异位症和非子宫内膜异位症女性的体液和子宫内膜组织的病例对照生物研究,并进行回顾性评估。
参与者/材料、设置和方法:在学术研究实验室中,从 58 名子宫内膜异位症女性和 28 名非子宫内膜异位症女性中收集 PF 和血清。从这些女性中的一部分收集月经血。在原代培养中分离 PF 中的巨噬细胞(Mφ)和在位子宫内膜的基质细胞。在细菌培养系统中检查 PGE(2)对大肠杆菌复制的外源影响。通过 ELISA 测量不同体液以及 Mφ和基质细胞培养物中 PGE(2)的水平。检查 PGE(2)对外周血淋巴细胞(PBL)生长的影响。
月经血中的 PGE(2)水平比血清或 PF 中的 PGE(2)水平高 2-3 倍。子宫内膜异位症女性的 MF 和 PF 中 PGE(2)水平明显高于对照组女性(P <0.05)。与未处理的细菌相比,外源性 PGE(2)处理以剂量依赖性方式增加大肠杆菌集落形成。富含 PGE(2)的 MF 能够以稀释依赖性方式刺激大肠杆菌的生长;与对照组女性相比,这种作用在子宫内膜异位症女性中增强更为显著(P <0.05)。子宫内膜异位症女性中 LPS 处理的 Mφ/基质细胞培养物中的 PGE(2)水平明显高于非子宫内膜异位症女性(P <0.05)。直接应用 PGE(2)和源自子宫内膜 Mφ或基质细胞的培养基显著抑制植物血凝素刺激的 PBL 生长。
需要进一步研究以检查 PGE(2)刺激的大肠杆菌生长与内毒素水平之间的关联,并研究阴道腔内可能发生的亚临床感染。
我们的发现可能为理解神秘疾病子宫内膜异位症的病理生理学或发病机制提供一些新的见解,并可能具有新的治疗潜力。
研究资助/利益冲突:这项工作得到了日本文部科学省科学研究补助金的支持。与这项研究没有利益冲突。
不适用。