Khan Khaleque N, Fujishita Akira, Hiraki Koichi, Kitajima Michio, Nakashima Masahiro, Fushiki Shinji, Kitawaki Jo
Graduate School of Medical Science Department of Obstetrics and Gynecology Kyoto Prefectural University of Medicine Kyoto Japan.
Department of Gynecology Saiseikai Nagasaki Hospital Nagasaki Japan.
Reprod Med Biol. 2018 Jan 18;17(2):125-133. doi: 10.1002/rmb2.12083. eCollection 2018 Apr.
Endometriosis is a multifactorial disease that mainly affects women of reproductive age. The exact pathogenesis of this disease is still debatable. The role of bacterial endotoxin (lipopolysaccharide, LPS) and Toll-like receptor 4 (TLR4) in endometriosis were investigated and the possible source of endotoxin in the pelvic environment was examined.
The limulus amoebocyte lysate test was used to measure the endotoxin levels in the menstrual fluid and peritoneal fluid and their potential role in the growth of endometriosis was investigated. Menstrual blood and endometrial samples were cultured for the presence of microbes. The effect of gonadotrophin-releasing hormone agonist (GnRHa) treatment on intrauterine microbial colonization (IUMC) and the occurrence of endometritis was investigated.
Lipopolysaccharide regulates the pro-inflammatory response in the pelvis and growth of endometriosis via the LPS/TLR4 cascade. The menstrual blood was highly contaminated with and the endometrial samples were colonized with other microbes. A cross-talk between inflammation and ovarian steroids or the stress reaction also was observed in the pelvis. Treatment with GnRHa further worsens intrauterine microbial colonization, with the consequent occurrence of endometritis in women with endometriosis.
For the first time, a new concept called the "bacterial contamination hypothesis" is proposed in endometriosis. This study's findings of IUMC in women with endometriosis could hold new therapeutic potential in addition to the conventional estrogen-suppressing agent.
子宫内膜异位症是一种多因素疾病,主要影响育龄女性。该疾病的确切发病机制仍存在争议。本研究探讨了细菌内毒素(脂多糖,LPS)和Toll样受体4(TLR4)在子宫内膜异位症中的作用,并检测了盆腔环境中内毒素的可能来源。
采用鲎试剂法检测月经液和腹腔液中的内毒素水平,并研究其在子宫内膜异位症生长中的潜在作用。对月经血和子宫内膜样本进行微生物培养。研究促性腺激素释放激素激动剂(GnRHa)治疗对子宫内微生物定植(IUMC)和子宫内膜炎发生的影响。
脂多糖通过LPS/TLR4级联反应调节盆腔中的促炎反应和子宫内膜异位症的生长。月经血受到高度污染,子宫内膜样本被其他微生物定植。在盆腔中还观察到炎症与卵巢类固醇或应激反应之间的相互作用。GnRHa治疗会进一步加重子宫内微生物定植,从而导致子宫内膜异位症患者发生子宫内膜炎。
本研究首次在子宫内膜异位症中提出了“细菌污染假说”这一新概念。本研究关于子宫内膜异位症患者IUMC的发现,除了传统的雌激素抑制剂外,可能具有新的治疗潜力。